Presidential Symposium will demonstrate how
proprietary computational pathology biomarker for TROP2 enhances
patient selection and potentially predicts patient outcomes in
advanced lung cancer
Presidential Symposium for NIAGARA will
highlight practice-changing impact of a perioperative
IMFINZI® (durvalumab)-based regimen in bladder cancer
AstraZeneca advances its ambition to revolutionize cancer care
with new data across its diverse, industry-leading portfolio and
pipeline at the IASLC 2024 World Conference on Lung Cancer (WCLC)
hosted by the International Association for the Study of Lung
Cancer, September 7 to 10, 2024 and the European Society for
Medical Oncology (ESMO) Congress, September 13 to 17, 2024.
Across the two meetings, more than 130 abstracts will feature 17
approved and potential new medicines from AstraZeneca including
five Presidential Symposia and 41 oral presentations.
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “The presentations across these two congresses
advance our long-term strategy to revolutionize cancer care. We
will show results from our computational pathology platform at WCLC
which we are using across our antibody drug conjugate portfolio to
develop predictive biomarkers to enhance patient selection and
improve outcomes for patients. We will also share data on the use
of our TROP2 antibody drug conjugate datopotamab deruxtecan in
combination with IMFINZI in early-stage lung cancer, a promising
first look at clinical activity from two of our own pipeline
antibody drug conjugates and important progress for our
next-generation immunotherapies.”
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, AstraZeneca, said: “Our data featured at WCLC and ESMO will
exhibit AstraZeneca’s progress in advancing several of the biggest
trends transforming cancer treatment today and potentially in the
future. Positive results for IMFINZI from the NIAGARA trial in
muscle-invasive bladder cancer will show the importance of
integrating perioperative immunotherapy in this setting, and data
for datopotamab deruxtecan and ENHERTU in several lung cancer
settings will highlight how antibody drug conjugates have the
potential to replace traditional chemotherapy approaches in many
cancer settings.”
Key trend: early intervention and transforming outcomes in
early-stage disease
A Presidential Symposium at ESMO will showcase the results from
the NIAGARA Phase III trial of IMFINZI® (durvalumab) in combination
with neoadjuvant chemotherapy before cystectomy (surgery to remove
the bladder) followed by IMFINZI as adjuvant monotherapy in
patients with muscle-invasive bladder cancer. High-level results
for this IMFINZI-based regimen showed a statistically significant
and clinically meaningful event-free survival (EFS) and overall
survival (OS) benefit, making it the first perioperative
immunotherapy regimen to show extended survival in bladder cancer
in a Phase III trial.
In lung cancer, several presentations at both meetings will
reinforce the Company’s progress toward moving treatment to earlier
stages of disease. These include:
- A late-breaking Presidential Symposium at WCLC that will
feature efficacy and safety data from the NeoCOAST-2 Phase II
platform trial. This trial evaluates IMFINZI in multiple novel
combinations, before and after surgery, in patients with
resectable, early-stage non-small cell lung cancer (NSCLC),
including a combination with datopotamab deruxtecan (Dato-DXd).
Results will build on the proven efficacy of perioperative IMFINZI
as demonstrated in the AEGEAN Phase III trial, which was recently
approved in the US.
- A late-breaking oral presentation at WCLC sharing results from
the second interim analysis of the AEGEAN Phase III trial of
perioperative IMFINZI-based treatment in patients with resectable
early-stage (IIA-IIIB) NSCLC. The data include EFS in subgroups of
patients who did or did not achieve pathologic complete response,
as well as new disease-free survival and OS results. An additional
late-breaking oral presentation at ESMO sharing AEGEAN circulating
tumor DNA (ctDNA) data will provide insights on how patients
respond to treatment.
- A late-breaking mini-oral presentation at WCLC highlighting
patient-reported outcomes from the ADRIATIC Phase III trial of
IMFINZI in patients with limited-stage small cell lung cancer whose
disease did not progress on concurrent chemoradiotherapy (CRT).
Additionally, an oral presentation at ESMO will share outcomes in
key patient subgroups.
- A mini-oral presentation at ESMO of results from the LAURA
Phase III trial including analyses of central nervous system
metastases and distant progression with TAGRISSO® (osimertinib) in
unresectable, Stage III EGFRm NSCLC after CRT. Additional data from
LAURA will include a safety analysis at WCLC and a poster
presentation at ESMO of efficacy and safety results in a cohort of
patients in China.
Key trend: novel ADCs replacing systemic chemotherapy
A late-breaking Presidential Symposium at WCLC of exploratory
results from the application of AstraZeneca’s proprietary
computational pathology platform, quantitative continuous scoring
(QCS), to tissue samples collected in TROPION-Lung01 will
demonstrate the potential of TROP2, as measured by QCS, as a
predictive biomarker for datopotamab deruxtecan.
Additionally, a late-breaking oral presentation will showcase OS
data from the TROPION-Lung01 Phase III trial evaluating datopotamab
deruxtecan in patients with previously treated locally advanced or
metastatic NSCLC. In May, high-level results showed that
datopotamab deruxtecan demonstrated a clinically meaningful OS
improvement versus docetaxel, the current standard-of-care
chemotherapy, in patients with advanced nonsquamous NSCLC
previously treated with immunotherapy or targeted therapy.
Also, at WCLC, an oral presentation will highlight efficacy and
safety data from Part 1 of the DESTINY-Lung03 Phase Ib trial of
ENHERTU® (fam-trastuzumab deruxtecan-nxki) in patients with
previously treated HER2-overexpressing unresectable, locally
advanced or metastatic NSCLC, building on data from the
DESTINY-Lung01 Phase II trial.
At ESMO, a late-breaking oral presentation from the
DESTINY-Breast12 Phase IIIb/IV trial of ENHERTU in patients with
previously treated metastatic HER2-positive breast cancer with and
without brain metastases will showcase the potential benefits of
this important medicine in this patient population. Additionally,
an oral presentation of the DESTINY-Gastric03 Phase Ib/II trial
will feature safety and efficacy data for the combination of
ENHERTU, chemotherapy and pembrolizumab as a 1st-line treatment in
HER2-positive gastric and gastroesophageal junction (GEJ)
cancers.
A mini-oral presentation at ESMO will highlight first results
from the endometrial and ovarian cancer cohorts of the
TROPION-PanTumor03 Phase II trial of datopotamab deruxtecan.
Several presentations at ESMO will showcase the strength of the
Company’s emerging proprietary antibody drug conjugate (ADC)
technology. These include:
- A proffered paper presentation sharing dose escalation results
from the BLUESTAR Phase I/IIa trial of B7-H4 ADC AZD8205 in
patients with B7-H4-expressing advanced solid tumors. B7-H4 is a
promising ADC target which is highly expressed in several solid
tumors. AZD8205 is the first ADC bearing a novel proprietary
topoisomerase I inhibitor (TOP1i) linker payload to enter the
clinic. Robust AZD8205 anti-tumor response has previously been
reported in B7-H4-expressing preclinical models across multiple
tumor types.
- A poster presentation sharing dose escalation results from the
FONTANA Phase I/IIa first-in-human trial of AZD5335 demonstrating
clinical activity, favorable pharmacokinetic and manageable safety
profiles in patients with platinum-resistant recurrent ovarian
cancer. This ADC has a FRα-targeting antibody linked to a
proprietary TOP1i warhead. A robust anti-tumor response has
previously been reported in FRα-expressing preclinical models that
are resistant to another FRα ADC with a microtubule inhibitor
warhead.
Key trend: advancing next wave of immunotherapy
agents
Several presentations will underscore the Company’s commitment
to advancing its comprehensive bispecific antibody program:
- A poster presentation sharing the first report of overall
response rate and safety data from Substudy 2 of the GEMINI-Gastric
Phase II trial, testing rilvegostomig (AZD2936), a PD-1/TIGIT
bispecific immune checkpoint inhibitor, plus chemotherapy as a
1st-line treatment in patients with HER2-negative, locally advanced
unresectable or metastatic GEJ cancers.
- Additionally, two late-breaking oral presentations at WCLC will
highlight efficacy and safety results from the ARTEMIDE-01 Phase I
trial of rilvegostomig in patients with metastatic NSCLC, as well
as from a Phase Ib/II trial of volrustomig (PD-1/CTLA-4) in
combination with chemotherapy in the 1st-line for patients with
advanced NSCLC.
Key trend: powerful combinations to attack cancer from
multiple angles
In addition to the novel regimens evaluated in DESTINY-Lung03,
DESTINY-Gastric03 and NeoCOAST-2, we are assessing further
combination treatment approaches below to improve outcomes for
patients:
- A late-breaking, Presidential Symposium presentation for
TAGRISSO from the externally sponsored FLOWERS Phase II trial of
TAGRISSO with or without savolitinib in patients with EGFRm
advanced NSCLC with MET aberrations will evaluate the potential of
this novel combination to overcome mechanisms of resistance in the
1st-line setting.
- Two late-breaking mini-oral presentations at WCLC will
highlight new data from the FLAURA2 Phase III trial of TAGRISSO
plus chemotherapy in advanced EGFRm NSCLC, including efficacy in
patients with high tumor burden and those whose cancers harbour
TP53 mutations at baseline.
- A mini-oral presentation featuring five-year OS data from an
exploratory analysis of the HIMALAYA Phase III trial of STRIDE
(Single Tremelimumab-actl Regular Interval Durvalumab) in patients
with unresectable liver cancer who have not received prior systemic
therapy and are not eligible for localized treatment. These data
represent the longest survival follow-up reported to date for a
Phase III trial in this setting.
Collaboration in the scientific community is critical to
improving outcomes for patients. AstraZeneca is collaborating with
Daiichi Sankyo Company Limited to develop and commercialize ENHERTU
and datopotamab deruxtecan, collaborating with Merck & Co.,
Inc. (known as MSD outside the US and Canada) to develop and
commercialize LYNPARZA® (olaparib), and collaborating with HUTCHMED
to develop and commercialize savolitinib. Rilvegostomig is a
PD-1/TIGIT bispecific antibody where the TIGIT component is derived
from Compugen’s clinical stage anti-TIGIT antibody, COM902.
AstraZeneca obtained full oncology rights to monalizumab from
Innate Pharma in October 2018 through a co-development and
commercialisation agreement initiated in 2015.
Key AstraZeneca presentations during IASLC WCLC 20241
Lead Author Abstract Title
Presentation details (PDT)
Antibody drug conjugates
Garassino, MC
Normalized membrane ratio of TROP2 by
quantitative continuous scoring is predictive of clinical outcomes
in TROPION-Lung 01
Abstract #PL02.11
Presidential 1
September 8, 2024
9:22 AM
Sands, J
Datopotamab deruxtecan vs docetaxel in
patients with non-small cell lung cancer: final overall survival
from TROPION-Lung01
Abstract #OA08.03
Oral Session
September 9, 2024
10:47 AM
Planchard, D
Fam-trastuzumab deruxtecan-nxki
monotherapy in pretreated HER2-overexpressing nonsquamous non-small
cell lung cancer: DESTINY-Lung03 part 1
Abstract #OA16.05
Oral Session
September 10, 2024
1:52 PM
Immuno-oncology
Cascone, T
Neocoast-2: Efficacy and safety of
neoadjuvant durvalumab (D) + novel anticancer agents + CT and
adjuvant D ± novel agents in resectable NSCLC
Abstract #PL02.07
Presidential 1 September 8, 2024
8:56 AM
Hiltermann, TJN
Efficacy and safety of rilvegostomig, an
anti-PD-1/TIGIT bispecific, for CPI-naïve metastatic NSCLC with
PD-L1 1-49% or ≥50%
Abstract #OA11.03
Oral Session
September 9, 2024
2:02 PM
Heymach, JV
Perioperative durvalumab for resectable
NSCLC (R-NSCLC): updated outcomes from the phase 3 AEGEAN trial
Abstract #OA13.03
Oral Session
September 9, 2024
3:32 PM
Spigel, DR
Volrustomig + platinum doublet
chemotherapy (CTx) in first-line non-small cell lung cancer
(NSCLC): phase 1b trial update
Abstract #OA11.04
Oral Session
September 9, 2024
2:12 PM
Novello, S
Patient-reported outcomes (PROs) with
consolidation durvalumab versus placebo following cCRT in
limited-stage SCLC: ADRIATIC
Abstract #MA17.04
Mini Oral Session
September 10, 2024
3:07 PM
Skoulidis, F
TRITON: Tremelimumab-actl + durvalumab +
chemotherapy (CT) vs pembrolizumab + CT in mNSCLC with STK11, KEAP1
and/or KRAS mutations
Abstract #P4.11D.01
Poster Session
September 9, 2024
6:30 PM
Tumor drivers and resistance
Yang, J
Osimertinib with or without savolitinib as
1L in de novo MET aberrant, EGFRm advanced NSCLC (CTONG 2008): a
phase II trial
Abstract #PL04.10
Presidential 2
September 9, 2024
9:17 AM
Kato, T
Osimertinib after definitive CRT in
unresectable stage III EGFR-mutated NSCLC: safety outcomes from the
phase 3 LAURA study
Abstract #OA12.03
Oral Session
September 9, 2024
2:02 PM
Yang, JC
FLAURA2: Resistance, and impact of
baseline TP53 alterations in patients treated with 1L osimertinib ±
platinum-pemetrexed
Abstract #MA12.03
Mini Oral Session
September 10, 2024
1:32 PM
Valdiviezo, N
FLAURA2: Impact of tumor burden on
outcomes of 1L osimertinib ± chemotherapy in patients with
EGFR-mutated advanced NSCLC
Abstract #MA12.04
Mini Oral Session
September 10, 2024
1:37 PM
1 59 abstracts at IASLC WCLC 2024 will
feature AstraZeneca medicines and pipeline molecules
Key AstraZeneca presentations during ESMO Congress
20242
Lead Author Abstract Title Presentation details
(CEST) Antibody drug conjugates
Datopotamab deruxtecan
Oaknin, A
Datopotamab deruxtecan (Dato-DXd) in
patients with endometrial (EC) or ovarian cancer (OC): results from
the phase 2 TROPION-PanTumor03 study
Abstract #714MO
Mini Oral Session
September 15, 2024
2:45 PM
Trivedi, MS
Rates of pathologic complete response
(pCR) after datopotamab deruxtecan (dato) plus durvalumab (durva)
treatment strategy in the neoadjuvant setting: results from the
I-SPY 2.2 trial
Abstract #LBA15
Mini Oral Session
September 14, 2024
11:20 AM
Khoury, K
Rates of pathologic complete response
(pCR) after datopotamab deruxtecan (dato) in the neoadjuvant
setting: results from the I-SPY 2.2 trial
Abstract #LBA16
Mini Oral Session
September 14, 2024
11:25 AM
Rugo, HS
Exposure-adjusted incidence rates (EAIRs)
of adverse events (AEs) from the TROPION-Breast01 study of
datopotamab deruxtecan (Dato-DXd) vs investigator’s choice of
chemotherapy (ICC) in patients (pts) with pretreated,
inoperable/metastatic HR+/HER2– breast cancer (BC)
Abstract #431P
Poster Session
September 16, 2024
Pons-Tostivint, E
Datopotamab deruxtecan (Dato-DXd) vs
docetaxel (DTX) in patients (pts) with advanced nonsquamous (NSQ)
non-small cell lung cancer (NSCLC) with brain metastases (mets):
results from TROPION-Lung01
Abstract #1312P
Poster Session
September 14, 2024
Enhertu
Lin, N
Fam-trastuzumab deruxtecan-nxki (T-DXd) in
patients (pts) with HER2+ advanced/metastatic breast cancer (mBC)
with or without brain metastases (BM): DESTINYBreast-12 primary
results
Abstract #LBA18
Proffered Paper Session
September 13, 2024
4:00 PM
Janjigian, YY
Fam-trastuzumab deruxtecan-nxki (T-DXd)
monotherapy and combinations in patients (pts) with
advanced/metastatic HER2-positive (HER2+) esophageal, gastric or
gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03
(DG-03)
Abstract #1401O
Proffered Paper Session
September 14, 2024
9:25 AM
Hu, X
Effects of fam-trastuzumab deruxtecan-nxki
(T-DXd) vs choice of chemotherapy (TPC) on patient-reported
outcomes (PROs) in hormone receptor–positive, HER2-low or
HER2-ultralow metastatic breast cancer (mBC): results from
DESTINY-Breast06
Abstract #LBA22
Mini Oral Session
September 15, 2024
9:10 AM
Ueno, NT
Exploratory biomarker analysis of
fam-trastuzumab deruxtecan-nxki versus treatment of physician’s
choice in HER2-low, hormone receptor–positive metastatic breast
cancer in DESTINY-Breast04
Abstract #432P
Poster Session
September 16, 2024
AZD8205
Meric-Bernstam, F
Initial results from a first-in-human
study of the B7-H4–directed antibody-drug conjugate (ADC) AZD8205
(puxitatug samrotecan) in patients with advanced/metastatic solid
tumors
Abstract #606O
Proffered Paper Session
September 13, 2024
4:50 PM
AZD5335
Shapira-Frommer, R
Initial results from a first-in-human
study of AZD5335, a folate receptor α (FRα)-targeted antibody-drug
conjugate, in patients (pts) with platinum-resistant recurrent
ovarian cancer (PRROC)
Abstract #754P
Poster Session
September 14, 2024
Immuno-oncology
Powles, TB
A randomized phase 3 trial of neoadjuvant
durvalumab plus chemotherapy followed by radical cystectomy and
adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA)
Abstract #LBA5
Presidential 2
September 15, 2024
5:14 PM
Tomasini, P
Precision immuno-oncology for advanced
non-small cell lung cancer (NSCLC) patients with PD-(L)1 inhibitors
resistance (PIONeeR): a phase Ib/IIa clinical trial targeting
identified resistance pathways
Abstract #LBA8
Presidential 3
September 16, 2024
5:24 PM
Senan, S
Durvalumab (D) as consolidation therapy in
limited-stage SCLC (LS-SCLC): outcomes by prior concurrent
chemoradiotherapy (cCRT) regimen and prophylactic cranial
irradiation (PCI) use in the ADRIATIC trial
Abstract #LBA81
Proffered Paper Session
September 13, 2024
2:25 PM
Reck, M
Associations of ctDNA clearance (CL)
during neoadjuvant Tx with pathological response and event-free
survival (EFS) in pts with resectable NSCLC (R-NSCLC): expanded
analyses from AEGEAN
Abstract #LBA49
Mini Oral Session
September 15, 2024
10:40 AM
Riccardo Filippi, A
Circulating tumor DNA (ctDNA) dynamics and
treatment responses in chemotherapy-ineligible patients (pts) with
unresectable Stage III NSCLC from the phase 2 DUART trial
Abstract #LBA51
Mini Oral Session
September 15, 2024
10:45 AM
Rimassa, L
Five-year overall survival (OS) and OS by
tumor response measures from the phase 3 HIMALAYA study of
tremelimumab-actl plus durvalumab in unresectable hepatocellular
carcinoma (uHCC)
Abstract #947MO
Mini Oral Session
September 16, 2024
9:25 AM
Rivera Herrero, F
First-line rilvegostomig (rilve) +
chemotherapy (CTx) in patients (pts) with HER2-negative (HER2–)
locally advanced unresectable or metastatic gastric cancers: first
report of GEMINI-Gastric substudy 2
Abstract #1422P
Poster Session
September 16, 2024
Blank, SV
Durvalumab + carboplatin/paclitaxel (CP)
followed by durvalumab ± olaparib as a first-line treatment for
endometrial cancer (EC): progression-free survival (PFS) by
clinical factors in DUO-E
Abstract #732P
Poster Session
September 14, 2024
Tumor drivers and resistance
Lu, S
Osimertinib (osi) after definitive
chemoradiotherapy (CRT) in unresectable (UR) stg III EGFRm NSCLC:
analyses of CNS and distant progression from the phase 3 LAURA
study
Abstract #1241MO
Mini Oral Session
September 16, 2024
2:45 PM
Dong, X
Osimertinib (osi) after definitive
chemoradiotherapy (CRT) in unresectable stage III epidermal growth
factor receptor-mutated (EGFRm) NSCLC: LAURA China cohort
analysis
Abstract #1248P
Poster Session
September 14, 2024
2 79 abstracts at ESMO Congress 2024 will
feature AstraZeneca medicines and pipeline molecules
IMPORTANT SAFETY INFORMATION FOR IMFINZI® and IMJUDO®
There are no contraindications for IMFINZI® (durvalumab) or
IMJUDO® (tremelimumab-actl).
Severe and Fatal Immune-Mediated Adverse Reactions
Important immune-mediated adverse reactions listed under
Warnings and Precautions may not include all possible severe and
fatal immune-mediated reactions. Immune-mediated adverse reactions,
which may be severe or fatal, can occur in any organ system or
tissue. Immune-mediated adverse reactions can occur at any time
after starting treatment or after discontinuation. Monitor patients
closely for symptoms and signs that may be clinical manifestations
of underlying immune-mediated adverse reactions. Evaluate clinical
chemistries including liver enzymes, creatinine,
adrenocorticotropic hormone (ACTH) level, and thyroid function at
baseline and before each dose. In cases of suspected
immune-mediated adverse reactions, initiate appropriate workup to
exclude alternative etiologies, including infection. Institute
medical management promptly, including specialty consultation as
appropriate. Withhold or permanently discontinue IMFINZI and IMJUDO
depending on severity. See USPI Dosing and Administration for
specific details. In general, if IMFINZI and IMJUDO requires
interruption or discontinuation, administer systemic corticosteroid
therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until
improvement to Grade 1 or less. Upon improvement to Grade 1 or
less, initiate corticosteroid taper and continue to taper over at
least 1 month. Consider administration of other systemic
immunosuppressants in patients whose immune-mediated adverse
reactions are not controlled with corticosteroid therapy.
Immune-Mediated
Pneumonitis
IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which
may be fatal. The incidence of pneumonitis is higher in patients
who have received prior thoracic radiation.
- IMFINZI as a Single Agent
- In patients who did not receive recent prior radiation, the
incidence of immune-mediated pneumonitis was 2.4% (34/1414),
including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions.
In patients who received recent prior radiation, the incidence of
pneumonitis (including radiation pneumonitis) in patients with
unresectable Stage III NSCLC following definitive chemoradiation
within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3%
(87/475) in patients receiving IMFINZI and 12.8% (30/234) in
patients receiving placebo. Of the patients who received IMFINZI
(475), 1.1% were fatal and 2.7% were Grade 3 adverse
reactions.
- The frequency and severity of immune-mediated pneumonitis in
patients who did not receive definitive chemoradiation prior to
IMFINZI were similar in patients who received IMFINZI as a single
agent or with ES-SCLC or BTC when given in combination with
chemotherapy.
- IMFINZI with IMJUDO
- Immune‑mediated pneumonitis occurred in 1.3% (5/388) of
patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and
Grade 3 (0.2%) adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated pneumonitis occurred in 3.5% (21/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including fatal (0.5%), and Grade 3
(1%) adverse reactions.
Immune-Mediated Colitis
IMFINZI with IMJUDO and platinum-based chemotherapy can cause
immune-mediated colitis, which may be fatal.
IMFINZI and IMJUDO can cause immune-mediated colitis that is
frequently associated with diarrhea. Cytomegalovirus (CMV)
infection/reactivation has been reported in patients with
corticosteroid-refractory immune-mediated colitis. In cases of
corticosteroid-refractory colitis, consider repeating infectious
workup to exclude alternative etiologies.
- IMFINZI as a Single Agent
- Immune-mediated colitis occurred in 2% (37/1889) of patients
receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%)
adverse reactions.
- IMFINZI with IMJUDO
- Immune‑mediated colitis or diarrhea occurred in 6% (23/388) of
patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%)
adverse reactions. Intestinal perforation has been observed in
other studies of IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated colitis occurred in 6.5% (39/596) of patients
receiving IMFINZI in combination with IMJUDO and platinum-based
chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse
reactions. Intestinal perforation and large intestine perforation
were reported in 0.1% of patients.
Immune-Mediated
Hepatitis
IMFINZI and IMJUDO can cause immune-mediated hepatitis, which
may be fatal.
- IMFINZI as a Single Agent
- Immune-mediated hepatitis occurred in 2.8% (52/1889) of
patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%)
and Grade 3 (1.4%) adverse reactions.
- IMFINZI with IMJUDO
- Immune‑mediated hepatitis occurred in 7.5% (29/388) of patients
receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4
(0.3%) and Grade 3 (4.1%) adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated hepatitis occurred in 3.9% (23/596) of patients
receiving IMFINZI in combination with IMJUDO and platinum-based
chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3
(2%) adverse reactions.
Immune-Mediated
Endocrinopathies
- Adrenal Insufficiency: IMFINZI and IMJUDO can cause
primary or secondary adrenal insufficiency. For Grade 2 or higher
adrenal insufficiency, initiate symptomatic treatment, including
hormone replacement as clinically indicated.
- IMFINZI as a Single Agent
- Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889)
of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated adrenal insufficiency occurred in 1.5% (6/388)
of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%)
adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated adrenal insufficiency occurred in 2.2% (13/596)
of patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.8%) adverse
reactions.
- Hypophysitis: IMFINZI and IMJUDO can cause
immune-mediated hypophysitis. Hypophysitis can present with acute
symptoms associated with mass effect such as headache, photophobia,
or visual field cuts. Hypophysitis can cause hypopituitarism.
Initiate symptomatic treatment including hormone replacement as
clinically indicated.
- IMFINZI as a Single Agent
- Grade 3 hypophysitis/hypopituitarism occurred in <0.1%
(1/1889) of patients who received IMFINZI.
- IMFINZI with IMJUDO
- Immune-mediated hypophysitis/hypopituitarism occurred in 1%
(4/388) of patients receiving IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated hypophysitis occurred in 1.3% (8/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.5%) adverse
reactions.
- Thyroid Disorders (Thyroiditis, Hyperthyroidism, and
Hypothyroidism): IMFINZI and IMJUDO can cause immune-mediated
thyroid disorders. Thyroiditis can present with or without
endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate
hormone replacement therapy for hypothyroidism or institute medical
management of hyperthyroidism as clinically indicated.
- IMFINZI as a Single Agent
- Immune-mediated thyroiditis occurred in 0.5% (9/1889) of
patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of
patients receiving IMFINZI.
- Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of
patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated thyroiditis occurred in 1.5% (6/388) of
patients receiving IMFINZI and IMJUDO.
- Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of
patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%)
adverse reactions.
- Immune-mediated hypothyroidism occurred in 11% (42/388) of
patients receiving IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated thyroiditis occurred in 1.2% (7/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy.
- Immune-mediated hyperthyroidism occurred in 5% (30/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.2%) adverse
reactions.
- Immune-mediated hypothyroidism occurred in 8.6% (51/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.5%) adverse
reactions.
- IMFINZI with Carboplatin and Paclitaxel
- Immune-mediated hypothyroidism occurred in 14% (34/235) of
patients receiving IMFINZI in combination with carboplatin and
paclitaxel.
- Type 1 Diabetes Mellitus, which can present with diabetic
ketoacidosis: Monitor patients for hyperglycemia or other signs
and symptoms of diabetes. Initiate treatment with insulin as
clinically indicated.
- IMFINZI as a Single Agent
- Grade 3 immune-mediated Type 1 diabetes mellitus occurred in
<0.1% (1/1889) of patients receiving IMFINZI.
- IMFINZI with IMJUDO
- Two patients (0.5%, 2/388) had events of hyperglycemia
requiring insulin therapy that had not resolved at last
follow-up.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated Type 1 diabetes mellitus occurred in 0.5%
(3/596) of patients receiving IMFINZI in combination with IMJUDO
and platinum-based chemotherapy including Grade 3 (0.3%) adverse
reactions.
Immune-Mediated Nephritis with Renal
Dysfunction
IMFINZI and IMJUDO can cause immune-mediated nephritis.
- IMFINZI as a Single Agent
- Immune-mediated nephritis occurred in 0.5% (10/1889) of
patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated nephritis occurred in 1% (4/388) of patients
receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse
reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated nephritis occurred in 0.7% (4/596) of patients
receiving IMFINZI in combination with IMJUDO and platinum-based
chemotherapy, including Grade 3 (0.2%) adverse reactions.
Immune-Mediated Dermatology
Reactions
IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis.
Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS),
drug rash with eosinophilia and systemic symptoms (DRESS), and
toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 and
CTLA-4 blocking antibodies. Topical emollients and/or topical
corticosteroids may be adequate to treat mild to moderate
non-exfoliative rashes.
- IMFINZI as a Single Agent
- Immune-mediated rash or dermatitis occurred in 1.8% (34/1889)
of patients receiving IMFINZI, including Grade 3 (0.4%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of
patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and
Grade 3 (1.5%) adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.3%) adverse
reactions.
Immune-Mediated
Pancreatitis
IMFINZI in combination with IMJUDO can cause immune-mediated
pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388)
of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%)
and Grade 3 (1.5%) adverse reactions.
Other Immune-Mediated Adverse
Reactions
The following clinically significant, immune-mediated adverse
reactions occurred at an incidence of less than 1% each in patients
who received IMFINZI and IMJUDO or were reported with the use of
other immune-checkpoint inhibitors.
- Cardiac/vascular: Myocarditis, pericarditis,
vasculitis.
- Nervous system: Meningitis, encephalitis, myelitis and
demyelination, myasthenic syndrome/myasthenia gravis (including
exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune
neuropathy.
- Ocular: Uveitis, iritis, and other ocular inflammatory
toxicities can occur. Some cases can be associated with retinal
detachment. Various grades of visual impairment to include
blindness can occur. If uveitis occurs in combination with other
immune-mediated adverse reactions, consider a
Vogt-Koyanagi-Harada-like syndrome, as this may require treatment
with systemic steroids to reduce the risk of permanent vision
loss.
- Gastrointestinal: Pancreatitis including increases in
serum amylase and lipase levels, gastritis, duodenitis.
- Musculoskeletal and connective tissue disorders:
Myositis/polymyositis, rhabdomyolysis and associated sequelae
including renal failure, arthritis, polymyalgia rheumatic.
- Endocrine: Hypoparathyroidism.
- Other (hematologic/immune): Hemolytic anemia, aplastic
anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory
response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ
transplant rejection, other transplant (including corneal graft)
rejection.
Infusion-Related Reactions
IMFINZI and IMJUDO can cause severe or life-threatening
infusion-related reactions. Monitor for signs and symptoms of
infusion-related reactions. Interrupt, slow the rate of, or
permanently discontinue IMFINZI and IMJUDO based on the severity.
See USPI Dosing and Administration for specific details. For Grade
1 or 2 infusion-related reactions, consider using pre-medications
with subsequent doses.
- IMFINZI as a Single Agent
- Infusion-related reactions occurred in 2.2% (42/1889) of
patients receiving IMFINZI, including Grade 3 (0.3%) adverse
reactions.
- IMFINZI with IMJUDO
- Infusion-related reactions occurred in 10 (2.6%) patients
receiving IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Infusion-related reactions occurred in 2.9% (17/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.3%) adverse
reactions.
Complications of Allogeneic HSCT after IMFINZI
Fatal and other serious complications can occur in patients who
receive allogeneic hematopoietic stem cell transplantation (HSCT)
before or after being treated with a PD-1/L-1 blocking antibody.
Transplant-related complications include hyperacute
graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic
veno-occlusive disease (VOD) after reduced intensity conditioning,
and steroid-requiring febrile syndrome (without an identified
infectious cause). These complications may occur despite
intervening therapy between PD-1/L-1 blockade and allogeneic HSCT.
Follow patients closely for evidence of transplant-related
complications and intervene promptly. Consider the benefit versus
risks of treatment with a PD-1/L-1 blocking antibody prior to or
after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on their mechanism of action and data from animal studies,
IMFINZI and IMJUDO can cause fetal harm when administered to a
pregnant woman. Advise pregnant women of the potential risk to a
fetus. In females of reproductive potential, verify pregnancy
status prior to initiating IMFINZI and IMJUDO and advise them to
use effective contraception during treatment with IMFINZI and
IMJUDO and for 3 months after the last dose of IMFINZI and
IMJUDO.
Lactation
There is no information regarding the presence of IMFINZI and
IMJUDO in human milk; however, because of the potential for serious
adverse reactions in breastfed infants from IMFINZI and IMJUDO,
advise women not to breastfeed during treatment and for 3 months
after the last dose.
Adverse Reactions
Unresectable Stage III NSCLC
- In patients with Stage III NSCLC in the PACIFIC study receiving
IMFINZI (n=475), the most common adverse reactions (≥20%) were
cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis
(34%), upper respiratory tract infections (26%), dyspnea (25%), and
rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%)
were pneumonia (7%) and pneumonitis/radiation pneumonitis
(3.4%).
- In patients with Stage III NSCLC in the PACIFIC study receiving
IMFINZI (n=475), discontinuation due to adverse reactions occurred
in 15% of patients in the IMFINZI arm. Serious adverse reactions
occurred in 29% of patients receiving IMFINZI. The most frequent
serious adverse reactions (≥2%) were pneumonitis or radiation
pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation
pneumonitis and fatal pneumonia occurred in <2% of patients and
were similar across arms.
Resectable NSCLC
- In patients with resectable NSCLC in the AEGEAN study, the most
common adverse reactions (occurring in ≥20% of patients) were
anemia, nausea, constipation, fatigue, musculoskeletal pain, and
rash.
- In patients with resectable NSCLC in the neoadjuvant phase of
the AEGEAN study receiving IMFINZI in combination with
platinum-containing chemotherapy (n=401), permanent discontinuation
of IMFINZI due to an adverse reaction occurred in 6.7% of patients.
Serious adverse reactions occurred in 21% of patients. The most
frequent (≥1%) serious adverse reactions were pneumonia (2.7%),
anemia (1.5%), myelosuppression (1.5%), vomiting (1.2%),
neutropenia (1%), and acute kidney injury (1%). Fatal adverse
reactions occurred in 2% of patients, including death due to
COVID-19 pneumonia (0.5%), sepsis (0.5%), myocarditis (0.2%),
decreased appetite (0.2%), hemoptysis (0.2%), and death not
otherwise specified (0.2%). Of the 401 IMFINZI treated patients who
received neoadjuvant treatment and 398 placebo-treated patients who
received neoadjuvant treatment, 1.7% (n=7) and 1% (n=4),
respectively, did not receive surgery due to adverse
reactions.
- In patients with resectable NSCLC in the adjuvant phase of the
AEGEAN study receiving IMFINZI as a single agent (n=265), permanent
discontinuation of IMFINZI due to an adverse reaction occurred in
8% of patients. Serious adverse reactions occurred in 13% of
patients. The most frequent serious adverse reactions reported in
>1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and
COVID-19 (1.1%). Four fatal adverse reactions occurred during the
adjuvant phase of the study, including COVID-19 pneumonia,
pneumonia aspiration, interstitial lung disease and aortic
aneurysm.
Metastatic NSCLC
- In patients with mNSCLC in the POSEIDON study receiving IMFINZI
and IMJUDO plus platinum-based chemotherapy (n=330), the most
common adverse reactions (occurring in ≥20% of patients) were
nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased
appetite (28%), rash (27%), and diarrhea (22%).
- In patients with mNSCLC in the POSEIDON study receiving IMFINZI
in combination with IMJUDO and platinum-based chemotherapy (n=330),
permanent discontinuation of IMFINZI or IMJUDO due to an adverse
reaction occurred in 17% of patients. Serious adverse reactions
occurred in 44% of patients, with the most frequent serious adverse
reactions reported in at least 2% of patients being pneumonia
(11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%),
pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse
reactions occurred in a total of 4.2% of patients.
Extensive-stage Small Cell Lung Cancer
- In patients with extensive-stage SCLC in the CASPIAN study
receiving IMFINZI plus chemotherapy (n=265), the most common
adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%),
and alopecia (31%). The most common Grade 3 or 4 adverse reaction
(≥3%) was fatigue/asthenia (3.4%).
- In patients with extensive-stage SCLC in the CASPIAN study
receiving IMFINZI plus chemotherapy (n=265), IMFINZI was
discontinued due to adverse reactions in 7% of the patients
receiving IMFINZI plus chemotherapy. Serious adverse reactions
occurred in 31% of patients receiving IMFINZI plus chemotherapy.
The most frequent serious adverse reactions reported in at least 1%
of patients were febrile neutropenia (4.5%), pneumonia (2.3%),
anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD
(1.1%). Fatal adverse reactions occurred in 4.9% of patients
receiving IMFINZI plus chemotherapy.
Locally Advanced or Metastatic Biliary Tract Cancers
- In patients with locally advanced or metastatic BTC in the
TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse
reactions (occurring in ≥20% of patients) were fatigue (42%),
nausea (40%), constipation (32%), decreased appetite (26%),
abdominal pain (24%), rash (23%), and pyrexia (20%).
- In patients with locally advanced or metastatic BTC in the
TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to
adverse reactions occurred in 6% of the patients receiving IMFINZI
plus chemotherapy. Serious adverse reactions occurred in 47% of
patients receiving IMFINZI plus chemotherapy. The most frequent
serious adverse reactions reported in at least 2% of patients were
cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and
acute kidney injury (2.4%). Fatal adverse reactions occurred in
3.6% of patients receiving IMFINZI plus chemotherapy. These include
ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients),
and upper gastrointestinal hemorrhage (2 patients).
Unresectable Hepatocellular Carcinoma
- In patients with unresectable HCC in the HIMALAYA study
receiving IMFINZI and IMJUDO (n=388), the most common adverse
reactions (occurring in ≥20% of patients) were rash (32%), diarrhea
(27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%),
and abdominal pain (20%).
- In patients with unresectable HCC in the HIMALAYA study
receiving IMFINZI and IMJUDO (n=388), serious adverse reactions
occurred in 41% of patients. Serious adverse reactions in >1% of
patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%),
pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury
(1.3%), and anemia (1.3%). Fatal adverse reactions occurred in 8%
of patients who received IMFINZI and IMJUDO, including death (1%),
hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis
(0.5%), hepatic failure (0.5%), and immune-mediated hepatitis
(0.5%). Permanent discontinuation of treatment regimen due to an
adverse reaction occurred in 14% of patients.
Primary advanced or Recurrent dMMR Endometrial Cancer
- In patients with advanced or recurrent dMMR endometrial cancer
in the DUO-E study receiving IMFINZI in combination with
carboplatin and paclitaxel followed by IMFINZI as a single-agent
(n=44), the most common adverse reactions, including laboratory
abnormalities (occurring in >20% of patients) were peripheral
neuropathy (61%), musculoskeletal pain (59%), nausea (59%),
alopecia (52%), fatigue (41%), abdominal pain (39%), constipation
(39%), rash (39%), decreased magnesium (36%), increased ALT (32%),
increased AST (30%), diarrhea (27%), vomiting (27%), cough (27%),
decreased potassium (25%), dyspnea (25%), headache (23%), increased
alkaline phosphatase (20%), and decreased appetite (18%). The most
common Grade 3 or 4 adverse reactions (≥3%) were constipation
(4.5%) and fatigue (4.5%).
- In patients with advanced or recurrent dMMR endometrial cancer
in the DUO-E study receiving IMFINZI in combination with
carboplatin and paclitaxel followed by IMFINZI as a single-agent
(n=44), permanent discontinuation of IMFINZI due to adverse
reactions occurred in 11% of patients. Serious adverse reactions
occurred in 30% of patients who received IMFINZI with carboplatin
and paclitaxel; the most common serious adverse reactions (≥4%)
were constipation (4.5%) and rash (4.5%).
The safety and effectiveness of IMFINZI and IMJUDO have not been
established in pediatric patients.
Indications:
IMFINZI, as a single agent, is indicated for the treatment of
adult patients with unresectable Stage III non-small cell lung
cancer (NSCLC) whose disease has not progressed following
concurrent platinum-based chemotherapy and radiation therapy.
IMFINZI in combination with platinum-containing chemotherapy as
neoadjuvant treatment, followed by IMFINZI continued as a single
agent as adjuvant treatment after surgery, is indicated for the
treatment of adult patients with resectable (tumors ≥4 cm and/or
node positive) NSCLC and no known epidermal growth factor receptor
(EGFR) mutations or anaplastic lymphoma kinase (ALK)
rearrangements.
IMFINZI, in combination with IMJUDO and platinum-based
chemotherapy, is indicated for the treatment of adult patients with
metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic
tumor aberrations.
IMFINZI, in combination with etoposide and either carboplatin or
cisplatin, is indicated for the first-line treatment of adult
patients with extensive-stage small cell lung cancer (ES-SCLC).
IMFINZI, in combination with gemcitabine and cisplatin, is
indicated for the treatment of adult patients with locally advanced
or metastatic biliary tract cancer (BTC).
IMFINZI in combination with IMJUDO is indicated for the
treatment of adult patients with unresectable hepatocellular
carcinoma (uHCC).
IMFINZI in combination with carboplatin and paclitaxel followed
by IMFINZI as a single agent is indicated for the treatment of
adult patients with primary advanced or recurrent endometrial
cancer that is mismatch repair deficient (dMMR).
Please see Full Prescribing Information including Medication
Guide for IMFINZI and IMJUDO.
IMPORTANT SAFETY INFORMATION FOR ENHERTU®
Indications:
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor
conjugate indicated for the treatment of adult patients with:
- Unresectable or metastatic HER2-positive (IHC 3+ or ISH
positive) breast cancer who have received a prior anti-HER2-based
regimen either: – In the metastatic setting, or – In the
neoadjuvant or adjuvant setting and have developed disease
recurrence during or within six months of completing therapy
- Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-)
breast cancer, as determined by an FDA-approved test, who have
received a prior chemotherapy in the metastatic setting or
developed disease recurrence during or within 6 months of
completing adjuvant chemotherapy
- Unresectable or metastatic non-small cell lung cancer (NSCLC)
whose tumors have activating HER2 (ERBB2) mutations, as detected by
an FDA-approved test, and who have received a prior systemic
therapy
This indication is approved under accelerated
approval based on objective response rate and duration of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in a confirmatory
trial.
- Locally advanced or metastatic HER2-positive (IHC 3+ or IHC
2+/ISH positive) gastric or gastroesophageal junction (GEJ)
adenocarcinoma who have received a prior trastuzumab-based
regimen
- Unresectable or metastatic HER2-positive (IHC3+) solid tumors
who have received prior systemic treatment and have no satisfactory
alternative treatment options This indication is approved under
accelerated approval based on objective response rate and duration
of response. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
a confirmatory trial.
WARNING: INTERSTITIAL LUNG DISEASE and
EMBRYO-FETAL TOXICITY
- Interstitial lung disease (ILD) and pneumonitis, including
fatal cases, have been reported with ENHERTU. Monitor for and
promptly investigate signs and symptoms including cough, dyspnea,
fever, and other new or worsening respiratory symptoms. Permanently
discontinue ENHERTU in all patients with Grade 2 or higher
ILD/pneumonitis. Advise patients of the risk and to immediately
report symptoms.
- Exposure to ENHERTU during pregnancy can cause embryo-fetal
harm. Advise patients of these risks and the need for effective
contraception.
Contraindications
None.
Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease
(ILD), including pneumonitis, can occur in patients treated with
ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has
been observed in patients with moderate renal impairment. Advise
patients to immediately report cough, dyspnea, fever, and/or any
new or worsening respiratory symptoms. Monitor patients for signs
and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate
patients with suspected ILD by radiographic imaging. Consider
consultation with a pulmonologist. For asymptomatic ILD/pneumonitis
(Grade 1), interrupt ENHERTU until resolved to Grade 0, then if
resolved in ≤28 days from date of onset, maintain dose. If resolved
in >28 days from date of onset, reduce dose one level. Consider
corticosteroid treatment as soon as ILD/pneumonitis is suspected
(e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic
ILD/pneumonitis (Grade 2 or greater), permanently discontinue
ENHERTU. Promptly initiate systemic corticosteroid treatment as
soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day
prednisolone or equivalent) and continue for at least 14 days
followed by gradual taper for at least 4 weeks.
HER2-Positive or HER2-Low Metastatic
Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC
3+) (5.4 mg/kg)
In patients with metastatic breast cancer, HER2-mutant NSCLC,
and other solid tumors treated with ENHERTU 5.4 mg/kg, ILD occurred
in 12% of patients. Median time to first onset was 5.5 months
(range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis
occurred in 1.0% of patients treated with ENHERTU.
HER2-Positive Locally Advanced or
Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive
gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD
occurred in 10% of patients. Median time to first onset was 2.8
months (range: 1.2 to 21).
Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in
patients treated with ENHERTU. Monitor complete blood counts prior
to initiation of ENHERTU and prior to each dose, and as clinically
indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC]
<1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade
2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5
x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then
reduce dose by one level. For febrile neutropenia (ANC <1.0 x
109/L and temperature >38.3º C or a sustained temperature of
≥38º C for more than 1 hour), interrupt ENHERTU until resolved,
then reduce dose by one level.
HER2-Positive or HER2-Low Metastatic
Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC
3+) (5.4 mg/kg)
In patients with metastatic breast cancer, HER2-mutant NSCLC,
and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease
in neutrophil count was reported in 63% of patients. Seventeen
percent had Grade 3 or 4 decreased neutrophil count. Median time to
first onset of decreased neutrophil count was 22 days (range: 2 to
939). Febrile neutropenia was reported in 1% of patients.
HER2-Positive Locally Advanced or
Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive
gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a
decrease in neutrophil count was reported in 72% of patients.
Fifty-one percent had Grade 3 or 4 decreased neutrophil count.
Median time to first onset of decreased neutrophil count was 16
days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of
patients.
Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of
developing left ventricular dysfunction. Left ventricular ejection
fraction (LVEF) decrease has been observed with anti-HER2
therapies, including ENHERTU. Assess LVEF prior to initiation of
ENHERTU and at regular intervals during treatment as clinically
indicated. Manage LVEF decrease through treatment interruption.
When LVEF is >45% and absolute decrease from baseline is 10-20%,
continue treatment with ENHERTU. When LVEF is 40-45% and absolute
decrease from baseline is <10%, continue treatment with ENHERTU
and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and
absolute decrease from baseline is 10-20%, interrupt ENHERTU and
repeat LVEF assessment within 3 weeks. If LVEF has not recovered to
within 10% from baseline, permanently discontinue ENHERTU. If LVEF
recovers to within 10% from baseline, resume treatment with ENHERTU
at the same dose. When LVEF is <40% or absolute decrease from
baseline is >20%, interrupt ENHERTU and repeat LVEF assessment
within 3 weeks. If LVEF of <40% or absolute decrease from
baseline of >20% is confirmed, permanently discontinue ENHERTU.
Permanently discontinue ENHERTU in patients with symptomatic
congestive heart failure. Treatment with ENHERTU has not been
studied in patients with a history of clinically significant
cardiac disease or LVEF <50% prior to initiation of
treatment.
HER2-Positive or HER2-Low Metastatic
Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC
3+) (5.4 mg/kg)
In patients with metastatic breast cancer, HER2-mutant NSCLC,
and other solid tumors treated with ENHERTU 5.4 mg/kg, LVEF
decrease was reported in 3.8% of patients, of which 0.6% were Grade
3.
HER2-Positive Locally Advanced or
Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive
gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no
clinical adverse events of heart failure were reported; however, on
echocardiography, 8% were found to have asymptomatic Grade 2
decrease in LVEF.
Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant
woman. Advise patients of the potential risks to a fetus. Verify
the pregnancy status of females of reproductive potential prior to
the initiation of ENHERTU. Advise females of reproductive potential
to use effective contraception during treatment and for 7 months
after the last dose of ENHERTU. Advise male patients with female
partners of reproductive potential to use effective contraception
during treatment with ENHERTU and for 4 months after the last dose
of ENHERTU.
Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L)
interrupt ENHERTU until resolved to Grade 1 or less, then maintain
dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L)
interrupt ENHERTU until resolved to Grade 1 or less, then reduce
dose by one level.
Adverse Reactions
HER2-Positive and HER2-Low Metastatic
Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC
3+) (5.4 mg/kg)
The pooled safety population reflects exposure to ENHERTU 5.4
mg/kg intravenously every 3 weeks in 1799 patients in Study
DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02,
DESTINY-Breast03, DESTINY-Breast04, DESTINY-Lung01, DESTINY-Lung02,
DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 65%
were exposed for >6 months and 38% were exposed for >1 year.
In this pooled safety population, the most common (≥20%) adverse
reactions, including laboratory abnormalities, were nausea (73%),
decreased white blood cell count (70%), decreased hemoglobin (66%),
decreased neutrophil count (63%), decreased lymphocyte count (58%),
fatigue (56%), decreased platelet count (48%), increased aspartate
aminotransferase (47%), increased alanine aminotransferase (43%),
vomiting (40%), increased blood alkaline phosphatase (38%),
alopecia (34%), constipation (33%), decreased appetite (32%),
decreased blood potassium (31%), diarrhea (29%), musculoskeletal
pain (24%), and abdominal pain (20%).
HER2-Positive Metastatic Breast
Cancer
DESTINY-Breast03
The safety of ENHERTU was evaluated in 257 patients with
unresectable or metastatic HER2-positive breast cancer who received
at least one dose of ENHERTU 5.4 mg/kg intravenously once every
three weeks in DESTINY-Breast03. The median duration of treatment
was 14 months (range: 0.7 to 30).
Serious adverse reactions occurred in 19% of patients receiving
ENHERTU. Serious adverse reactions in >1% of patients who
received ENHERTU were vomiting, interstitial lung disease,
pneumonia, pyrexia, and urinary tract infection. Fatalities due to
adverse reactions occurred in 0.8% of patients including COVID-19
and sudden death (one patient each).
ENHERTU was permanently discontinued in 14% of patients, of
which ILD/pneumonitis accounted for 8%. Dose interruptions due to
adverse reactions occurred in 44% of patients treated with ENHERTU.
The most frequent adverse reactions (>2%) associated with dose
interruption were neutropenia, leukopenia, anemia,
thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis.
Dose reductions occurred in 21% of patients treated with ENHERTU.
The most frequent adverse reactions (>2%) associated with dose
reduction were nausea, neutropenia, and fatigue.
The most common (≥20%) adverse reactions, including laboratory
abnormalities, were nausea (76%), decreased white blood cell count
(74%), decreased neutrophil count (70%), increased aspartate
aminotransferase (67%), decreased hemoglobin (64%), decreased
lymphocyte count (55%), increased alanine aminotransferase (53%),
decreased platelet count (52%), fatigue (49%), vomiting (49%),
increased blood alkaline phosphatase (49%), alopecia (37%),
decreased blood potassium (35%), constipation (34%),
musculoskeletal pain (31%), diarrhea (29%), decreased appetite
(29%), headache (22%), respiratory infection (22%), abdominal pain
(21%), increased blood bilirubin (20%), and stomatitis (20%).
HER2-Low Metastatic Breast
Cancer
DESTINY-Breast04
The safety of ENHERTU was evaluated in 371 patients with
unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast
cancer who received ENHERTU 5.4 mg/kg intravenously once every 3
weeks in DESTINY-Breast04. The median duration of treatment was 8
months (range: 0.2 to 33) for patients who received ENHERTU.
Serious adverse reactions occurred in 28% of patients receiving
ENHERTU. Serious adverse reactions in >1% of patients who
received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea,
musculoskeletal pain, sepsis, anemia, febrile neutropenia,
hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to
adverse reactions occurred in 4% of patients including
ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic
colitis, disseminated intravascular coagulation, dyspnea, febrile
neutropenia, general physical health deterioration, pleural
effusion, and respiratory failure (1 patient each).
ENHERTU was permanently discontinued in 16% of patients, of
which ILD/pneumonitis accounted for 8%. Dose interruptions due to
adverse reactions occurred in 39% of patients treated with ENHERTU.
The most frequent adverse reactions (>2%) associated with dose
interruption were neutropenia, fatigue, anemia, leukopenia,
COVID-19, ILD/pneumonitis, increased transaminases, and
hyperbilirubinemia. Dose reductions occurred in 23% of patients
treated with ENHERTU. The most frequent adverse reactions (>2%)
associated with dose reduction were fatigue, nausea,
thrombocytopenia, and neutropenia.
The most common (≥20%) adverse reactions, including laboratory
abnormalities, were nausea (76%), decreased white blood cell count
(70%), decreased hemoglobin (64%), decreased neutrophil count
(64%), decreased lymphocyte count (55%), fatigue (54%), decreased
platelet count (44%), alopecia (40%), vomiting (40%), increased
aspartate aminotransferase (38%), increased alanine
aminotransferase (36%), constipation (34%), increased blood
alkaline phosphatase (34%), decreased appetite (32%),
musculoskeletal pain (32%), diarrhea (27%), and decreased blood
potassium (25%).
HER2-Mutant Unresectable or Metastatic
NSCLC (5.4 mg/kg)
DESTINY-Lung02 evaluated two dose levels (5.4 mg/kg [n=101] and
6.4 mg/kg [n=50]); however, only the results for the recommended
dose of 5.4 mg/kg intravenously every 3 weeks are described below
due to increased toxicity observed with the higher dose in patients
with NSCLC, including ILD/pneumonitis.
The safety of ENHERTU was evaluated in 101 patients with
HER2-mutant unresectable or metastatic NSCLC who received ENHERTU
5.4 mg/kg intravenously once every three weeks until disease
progression or unacceptable toxicity in DESTINY‑Lung02. Nineteen
percent of patients were exposed for >6 months.
Serious adverse reactions occurred in 30% of patients receiving
ENHERTU. Serious adverse reactions in >1% of patients who
received ENHERTU were ILD/pneumonitis, thrombocytopenia, dyspnea,
nausea, pleural effusion, and increased troponin I. Fatality
occurred in 1 patient with suspected ILD/pneumonitis (1%).
ENHERTU was permanently discontinued in 8% of patients. Adverse
reactions which resulted in permanent discontinuation of ENHERTU
were ILD/pneumonitis, diarrhea, decreased blood potassium,
hypomagnesemia, myocarditis, and vomiting. Dose interruptions of
ENHERTU due to adverse reactions occurred in 23% of patients.
Adverse reactions which required dose interruption (>2%)
included neutropenia and ILD/pneumonitis. Dose reductions due to an
adverse reaction occurred in 11% of patients.
The most common (≥20%) adverse reactions, including laboratory
abnormalities, were nausea (61%), decreased white blood cell count
(60%), decreased hemoglobin (58%), decreased neutrophil count
(52%), decreased lymphocyte count (43%), decreased platelet count
(40%), decreased albumin (39%), increased aspartate
aminotransferase (35%), increased alanine aminotransferase (34%),
fatigue (32%), constipation (31%), decreased appetite (30%),
vomiting (26%), increased alkaline phosphatase (22%), and alopecia
(21%).
HER2-Positive Locally Advanced or
Metastatic Gastric Cancer (6.4 mg/kg)
The safety of ENHERTU was evaluated in 187 patients with locally
advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma
in DESTINY-Gastric01. Patients intravenously received at least one
dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either
irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2
weekly for 3 weeks. The median duration of treatment was 4.6 months
(range: 0.7 to 22.3) for patients who received ENHERTU.
Serious adverse reactions occurred in 44% of patients receiving
ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients
who received ENHERTU were decreased appetite, ILD, anemia,
dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor
hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of
patients: disseminated intravascular coagulation, large intestine
perforation, and pneumonia occurred in one patient each (0.8%).
ENHERTU was permanently discontinued in 15% of patients, of
which ILD accounted for 6%. Dose interruptions due to adverse
reactions occurred in 62% of patients treated with ENHERTU. The
most frequent adverse reactions (>2%) associated with dose
interruption were neutropenia, anemia, decreased appetite,
leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia,
upper respiratory tract infection, diarrhea, and decreased blood
potassium. Dose reductions occurred in 32% of patients treated with
ENHERTU. The most frequent adverse reactions (>2%) associated
with dose reduction were neutropenia, decreased appetite, fatigue,
nausea, and febrile neutropenia.
The most common (≥20%) adverse reactions, including laboratory
abnormalities, were decreased hemoglobin (75%), decreased white
blood cell count (74%), decreased neutrophil count (72%), decreased
lymphocyte count (70%), decreased platelet count (68%), nausea
(63%), decreased appetite (60%), increased aspartate
aminotransferase (58%), fatigue (55%), increased blood alkaline
phosphatase (54%), increased alanine aminotransferase (47%),
diarrhea (32%), decreased blood potassium (30%), vomiting (26%),
constipation (24%), increased blood bilirubin (24%), pyrexia (24%),
and alopecia (22%).
HER2-Positive (IHC3+) Unresectable or
Metastatic Solid Tumors
The safety of ENHERTU was evaluated in 347 adult patients with
unresectable or metastatic HER2-positive (IHC3+) solid tumors who
received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in
DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01, and
DESTINY-CRC02. The median duration of treatment was 8.3 months
(range 0.7 to 30.2).
Serious adverse reactions occurred in 34% of patients receiving
ENHERTU. Serious adverse reactions in >1% of patients who
received ENHERTU were sepsis, pneumonia, vomiting, urinary tract
infection, abdominal pain, nausea, pneumonitis, pleural effusion,
hemorrhage, COVID-19, fatigue, acute kidney injury, anemia,
cellulitis, and dyspnea. Fatalities due to adverse reactions
occurred in 6.3% of patients including ILD/pneumonitis (2.3%),
cardiac arrest (0.6%), COVID-19 (0.6%), and sepsis (0.6%). The
following events occurred in one patient each (0.3%): acute kidney
injury, cerebrovascular accident, general physical health
deterioration, pneumonia, and hemorrhagic shock.
ENHERTU was permanently discontinued in 15% of patients, of
which ILD/pneumonitis accounted for 10%. Dose interruptions due to
adverse reactions occurred in 48% of patients. The most frequent
adverse reactions (>2%) associated with dose interruption were
decreased neutrophil count, anemia, COVID-19, fatigue, decreased
white blood cell count, and ILD/pneumonitis. Dose reductions
occurred in 27% of patients treated with ENHERTU. The most frequent
adverse reactions (>2%) associated with dose reduction were
fatigue, nausea, decreased neutrophil count, ILD/pneumonitis, and
diarrhea.
The most common (≥20%) adverse reactions, including laboratory
abnormalities, were decreased white blood cell count (75%), nausea
(69%), decreased hemoglobin (67%), decreased neutrophil count
(66%), fatigue (59%), decreased lymphocyte count (58%), decreased
platelet count (51%), increased aspartate aminotransferase (45%),
increased alanine aminotransferase (44%), increased blood alkaline
phosphatase (36%), vomiting (35%), decreased appetite (34%),
alopecia (34%), diarrhea (31%), decreased blood potassium (29%),
constipation (28%), decreased sodium (22%), stomatitis (20%), and
upper respiratory tract infection (20%).
Use in Specific Populations
- Pregnancy: ENHERTU can cause fetal harm when
administered to a pregnant woman. Advise patients of the potential
risks to a fetus. There are clinical considerations if ENHERTU is
used in pregnant women, or if a patient becomes pregnant within 7
months after the last dose of ENHERTU.
- Lactation: There are no data regarding the presence of
ENHERTU in human milk, the effects on the breastfed child, or the
effects on milk production. Because of the potential for serious
adverse reactions in a breastfed child, advise women not to
breastfeed during treatment with ENHERTU and for 7 months after the
last dose.
- Females and Males of Reproductive Potential:
Pregnancy testing: Verify pregnancy
status of females of reproductive potential prior to initiation of
ENHERTU. Contraception: Females:
ENHERTU can cause fetal harm when administered to a pregnant woman.
Advise females of reproductive potential to use effective
contraception during treatment with ENHERTU and for 7 months after
the last dose. Males: Advise male patients with female partners of
reproductive potential to use effective contraception during
treatment with ENHERTU and for 4 months after the last dose.
Infertility: ENHERTU may impair male
reproductive function and fertility.
- Pediatric Use: Safety and effectiveness of ENHERTU have
not been established in pediatric patients.
- Geriatric Use: Of the 1287 patients with HER2-positive
or HER2-low breast cancer treated with ENHERTU 5.4 mg/kg, 22% were
≥65 years and 3.8% were ≥75 years. No overall differences in
efficacy within clinical studies were observed between patients ≥65
years of age compared to younger patients. There was a higher
incidence of Grade 3-4 adverse reactions observed in patients aged
≥65 years (59%) as compared to younger patients (49%). Of the 101
patients with HER2-mutant unresectable or metastatic NSCLC treated
with ENHERTU 5.4 mg/kg, 40% were ≥65 years and 8% were ≥75 years.
No overall differences in efficacy or safety were observed between
patients ≥65 years of age compared to younger patients. Of the 125
patients with HER2-positive locally advanced or metastatic gastric
or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in
DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No
overall differences in efficacy or safety were observed between
patients ≥65 years of age compared to younger patients. Of the 192
patients with HER2-positive (IHC 3+) unresectable or metastatic
solid tumors treated with ENHERTU 5.4 mg/kg in DESTINY-PanTumor02,
DESTINY-Lung01, or DESTINY-CRC02, 39% were 65 years or older and 9%
were 75 years or older. No overall differences in efficacy or
safety were observed between patients ≥65 years of age compared to
younger patients.
- Renal Impairment: A higher incidence of Grade 1 and 2
ILD/pneumonitis has been observed in patients with moderate renal
impairment. Monitor patients with moderate renal impairment more
frequently. The recommended dosage of ENHERTU has not been
established for patients with severe renal impairment (CLcr <30
mL/min).
- Hepatic Impairment: In patients with moderate hepatic
impairment, due to potentially increased exposure, closely monitor
for increased toxicities related to the topoisomerase inhibitor,
DXd. The recommended dosage of ENHERTU has not been established for
patients with severe hepatic impairment (total bilirubin >3
times ULN and any AST).
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi
Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or
fda.gov/medwatch.
Please see accompanying full Prescribing
Information, including Boxed WARNINGS, and Medication
Guide.
IMPORTANT SAFETY INFORMATION FOR TAGRISSO®
There are no contraindications for TAGRISSO® (osimertinib).
- Interstitial lung disease (ILD)/pneumonitis occurred in 4% of
the 1813 TAGRISSO-treated patients; 0.4% of cases were fatal. In
the FLAURA2 study, ILD/pneumonitis occurred in 3.3% of the 276
patients who received TAGRISSO in combination with pemetrexed and
platinum-based chemotherapy; 0.4% of cases were fatal. Withhold
TAGRISSO and promptly investigate for ILD in patients who present
with worsening of respiratory symptoms which may be indicative of
ILD (eg, dyspnea, cough and fever). Permanently discontinue
TAGRISSO if ILD/pneumonitis is confirmed
- Heart rate-corrected QT (QTc) interval prolongation occurs in
TAGRISSO-treated patients. Of the 1813 TAGRISSO monotherapy-treated
patients in clinical trials, 1.1% were found to have a QTc >500
msec, and 4.3% of patients had an increase from baseline QTc >60
msec. Of the 276 patients treated with TAGRISSO in combination with
pemetrexed and platinum-based chemotherapy in the FLAURA2 study,
1.8% were found to have a QTc >500 msec, and 10.5% of patients
had an increase from baseline QTc >60 msec. No QTc-related
arrhythmias were reported. Conduct periodic monitoring with ECGs
and electrolytes in patients with congenital long QTc syndrome,
congestive heart failure, electrolyte abnormalities, or those who
are taking medications known to prolong the QTc interval.
Permanently discontinue TAGRISSO in patients who develop QTc
interval prolongation with signs/symptoms of life-threatening
arrhythmia
- Cardiomyopathy occurred in 3.8% of the 1813 TAGRISSO-treated
patients; 0.1% of cardiomyopathy cases were fatal. In the FLAURA2
study, cardiomyopathy occurred in 9% of the 276 patients who
received TAGRISSO in combination with pemetrexed and platinum-based
chemotherapy; 1.1% of cardiomyopathy cases were fatal. A decline in
left ventricular ejection fraction (LVEF) ≥10% from baseline and to
<50% LVEF occurred in 4.2% of 1557 patients who had baseline and
at least one follow-up LVEF assessment. In the ADAURA study, 1.5%
(5/325) of TAGRISSO-treated patients experienced LVEF decreases
≥10% from baseline and a drop to <50%. In the FLAURA2 study, 8%
(21/262) of patients treated with TAGRISSO in combination with
pemetrexed and platinum-based chemotherapy, who had baseline and at
least one follow-up LVEF assessment, experienced LVEF decreases
≥10% and a drop to less than 50%. For patients receiving TAGRISSO
monotherapy, conduct cardiac monitoring in patients with cardiac
risk factors, including assessment of LVEF at baseline and during
treatment. For patients receiving TAGRISSO in combination with
pemetrexed and platinum-based chemotherapy, conduct cardiac
monitoring in all patients, including assessment of LVEF at
baseline and during treatment. Assess LVEF in patients who develop
relevant cardiac signs or symptoms during treatment. For
symptomatic congestive heart failure, permanently discontinue
TAGRISSO
- Keratitis was reported in 0.6% of 1813 patients treated with
TAGRISSO monotherapy in clinical trials. Promptly refer patients
with signs and symptoms suggestive of keratitis (such as eye
inflammation, lacrimation, light sensitivity, blurred vision, eye
pain and/or red eye) to an ophthalmologist
- Postmarketing cases consistent with erythema multiforme major
(EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal
necrolysis (TEN) have been reported in patients receiving TAGRISSO.
Withhold TAGRISSO if EMM, SJS, or TEN is suspected and permanently
discontinue if confirmed
- Postmarketing cases of cutaneous vasculitis including
leukocytoclastic vasculitis, urticarial vasculitis, and IgA
vasculitis have been reported in patients receiving TAGRISSO.
Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate
for systemic involvement, and consider dermatology consultation. If
no other etiology can be identified, consider permanent
discontinuation of TAGRISSO based on severity
- Aplastic anemia has been reported in patients treated with
TAGRISSO in clinical trials (0.06% of 1813) and postmarketing. Some
cases had a fatal outcome. Inform patients of the signs and
symptoms of aplastic anemia including but not limited to, new or
persistent fevers, bruising, bleeding, and pallor. If aplastic
anemia is suspected, withhold TAGRISSO and obtain a hematology
consultation. If aplastic anemia is confirmed, permanently
discontinue TAGRISSO. Perform complete blood count with
differential before starting TAGRISSO, periodically throughout
treatment, and more frequently if indicated
- Verify pregnancy status of females of reproductive potential
prior to initiating TAGRISSO. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential
to use effective contraception during treatment with TAGRISSO and
for 6 weeks after the final dose. Advise males with female partners
of reproductive potential to use effective contraception for 4
months after the final dose
- Because of the potential for serious adverse reactions in
breastfed infants from TAGRISSO, women should not breastfeed during
treatment with TAGRISSO and for 2 weeks after the final dose
- Most common (≥20%) adverse reactions, including laboratory
abnormalities, were:
- TAGRISSO monotherapy: leukopenia, lymphopenia,
thrombocytopenia, anemia, diarrhea, rash, musculoskeletal pain,
neutropenia, nail toxicity, dry skin, stomatitis, and fatigue
- TAGRISSO in combination with pemetrexed and platinum-based
chemotherapy: leukopenia, thrombocytopenia, neutropenia,
lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin,
and increased blood creatinine
Indications:
- TAGRISSO is indicated as adjuvant therapy after tumor resection
in adult patients with non-small cell lung cancer (NSCLC) whose
tumors have epidermal growth factor receptor (EGFR) exon 19
deletions or exon 21 L858R mutations, as detected by an
FDA-approved test
- TAGRISSO is indicated for the first-line treatment of adult
patients with metastatic non-small cell lung cancer (NSCLC) whose
tumors have epidermal growth factor receptor (EGFR) exon 19
deletions or exon 21 L858R mutations, as detected by an
FDA-approved test
- TAGRISSO is indicated in combination with pemetrexed and
platinum-based chemotherapy, for the first-line treatment of adult
patients with locally advanced or metastatic NSCLC whose tumors
have epidermal growth factor receptor (EGFR) exon 19 deletions or
exon 21 L858R mutations, as detected by an FDA-approved test
- TAGRISSO is indicated for the treatment of adult patients with
metastatic epidermal growth factor receptor (EGFR) T790M
mutation-positive NSCLC, as detected by an FDA-approved test, whose
disease has progressed on or after EGFR tyrosine kinase inhibitor
(TKI) therapy
Please see complete Prescribing Information,
including Patient Information for TAGRISSO.
IMPORTANT SAFETY INFORMATION FOR LYNPARZA® (olaparib)
CONTRAINDICATIONS
There are no contraindications for LYNPARZA.
WARNINGS AND PRECAUTIONS
Myelodysplastic Syndrome/Acute Myeloid Leukemia
(MDS/AML): Occurred in approximately 1.2% of patients with
various BRCAm, gBRCAm, HRR gene-mutated or HRD-positive cancers who
received LYNPARZA as a single agent or as part of a combination
regimen, consistent with the approved indications, and the majority
of events had a fatal outcome. The median duration of therapy in
patients who developed MDS/AML was approximately 2 years (range:
<6 months to >4 years). All of these patients had previous
chemotherapy with platinum agents and/or other DNA-damaging agents,
including radiotherapy.
In SOLO-1, patients with newly diagnosed advanced BRCAm ovarian
cancer, the incidence of MDS/AML was 1.9% (5/260) in patients who
received LYNPARZA and 0.8% (1/130) in patients who received placebo
based on an updated analysis. In PAOLA-1, of patients with newly
diagnosed advanced ovarian cancer with HRD-positive status, the
incidence of MDS/AML was 1.6% (4/255) in patients who received
LYNPARZA and 2.3% (3/131) in the control arm.
In SOLO-2, patients with BRCAm platinum-sensitive relapsed
ovarian cancer, the incidence of MDS/AML was 8% (15/195) in
patients who received LYNPARZA and 4% (4/99) in patients who
received placebo. The duration of LYNPARZA treatment prior to the
diagnosis of MDS/AML ranged from 0.6 years to 4.5 years.
Do not start LYNPARZA until patients have recovered from
hematological toxicity caused by previous chemotherapy (≤Grade 1).
Monitor complete blood count for cytopenia at baseline and monthly
thereafter for clinically significant changes during treatment. For
prolonged hematological toxicities, interrupt LYNPARZA and monitor
blood count weekly until recovery.
If the levels have not recovered to Grade 1 or less after 4
weeks, refer the patient to a hematologist for further
investigations, including bone marrow analysis and blood sample for
cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.
Pneumonitis: Occurred in 0.8% of patients exposed to
LYNPARZA monotherapy, and some cases were fatal. If patients
present with new or worsening respiratory symptoms such as dyspnea,
cough, and fever, or a radiological abnormality occurs, interrupt
LYNPARZA treatment and initiate prompt investigation. Discontinue
LYNPARZA if pneumonitis is confirmed and treat patient
appropriately.
Venous Thromboembolism (VTE): Including severe or fatal
pulmonary embolism (PE) occurred in patients treated with LYNPARZA.
In the combined data of two randomized, placebo-controlled clinical
studies (PROfound and PROpel) in patients with metastatic
castration-resistant prostate cancer (N=1180), VTE occurred in 8%
of patients who received LYNPARZA, including pulmonary embolism in
6%. In the control arms, VTE occurred in 2.5%, including pulmonary
embolism in 1.5%. Monitor patients for signs and symptoms of venous
thrombosis and pulmonary embolism, and treat as medically
appropriate, which may include long-term anticoagulation as
clinically indicated.
Embryo-Fetal Toxicity: Based on its mechanism of action
and findings in animals, LYNPARZA can cause fetal harm. Verify
pregnancy status in females of reproductive potential prior to
initiating treatment.
Females
Advise females of reproductive potential of the potential risk
to a fetus and to use effective contraception during treatment and
for 6 months following the last dose.
Males
Advise male patients with female partners of reproductive
potential or who are pregnant to use effective contraception during
treatment and for 3 months following the last dose of LYNPARZA and
to not donate sperm during this time.
ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced
Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients
who received LYNPARZA in the first-line maintenance setting
for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain
(45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation
(28%), upper respiratory tract
infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia
(26%), decreased appetite (20%), dizziness (20%), neutropenia
(17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary
tract infection (13%), thrombocytopenia (11%), and stomatitis
(11%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA in the first-line maintenance
setting for SOLO-1 were: decrease in hemoglobin (87%),
increase in mean corpuscular volume (87%), decrease in leukocytes
(70%), decrease in lymphocytes (67%), decrease in absolute
neutrophil count (51%), decrease in platelets (35%), and increase
in serum creatinine (34%).
ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian
Cancer in Combination with Bevacizumab
Most common adverse reactions (Grades 1-4) in ≥10% of patients
treated with LYNPARZA/bevacizumab and at a ≥5% frequency compared
to placebo/bevacizumab in the first-line maintenance setting
for PAOLA-1 were: nausea (53%), fatigue (including asthenia)
(53%), anemia (41%), lymphopenia (24%), vomiting (22%), and
leukopenia (18%). In addition, the most common adverse reactions
(≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of
the frequency compared with the placebo/bevacizumab arm were:
diarrhea (18%), neutropenia (18%), urinary tract infection (15%),
and headache (14%).
In addition, venous thromboembolism occurred more commonly in
patients receiving LYNPARZA/bevacizumab (5%) than in those
receiving placebo/bevacizumab (1.9%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients for LYNPARZA in combination with bevacizumab in the
first-line maintenance setting for PAOLA-1 were:
decrease in hemoglobin (79%), decrease in lymphocytes (63%),
increase in serum creatinine (61%), decrease in leukocytes (59%),
decrease in absolute neutrophil count (35%), and decrease in
platelets (35%).
ADVERSE REACTIONS—Maintenance gBRCAm Recurrent Ovarian
Cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients
who received LYNPARZA in the maintenance setting for
SOLO-2 were: nausea (76%), fatigue (including asthenia)
(66%), anemia (44%), vomiting (37%), nasopharyngitis/upper
respiratory tract infection (URI)/influenza (36%), diarrhea (33%),
arthralgia/myalgia (30%), dysgeusia (27%), headache (26%),
decreased appetite (22%), and stomatitis (20%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA in the maintenance setting
for SOLO-2 were: increase in mean corpuscular volume (89%),
decrease in hemoglobin (83%), decrease in leukocytes (69%),
decrease in lymphocytes (67%), decrease in absolute neutrophil
count (51%), increase in serum creatinine (44%), and decrease in
platelets (42%).
ADVERSE REACTIONS—Adjuvant Treatment of gBRCAm,
HER2-Negative, High-Risk Early Breast Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients
who received LYNPARZA in the adjuvant setting for
OlympiA were: nausea (57%), fatigue (including asthenia)
(42%), anemia (24%), vomiting (23%), headache (20%), diarrhea
(18%), leukopenia (17%), neutropenia (16%), decreased appetite
(13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA in the adjuvant setting for
OlympiA were: decrease in lymphocytes (77%), increase in
mean corpuscular volume (67%), decrease in hemoglobin (65%),
decrease in leukocytes (64%), and decrease in absolute neutrophil
count (39%).
ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast
Cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients
who received LYNPARZA in the metastatic setting for
OlympiAD were: nausea (58%), anemia (40%), fatigue
(including asthenia) (37%), vomiting (30%), neutropenia (27%),
respiratory tract infection (27%), leukopenia (25%), diarrhea
(21%), and headache (20%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA in the metastatic setting for
OlympiAD were: decrease in hemoglobin (82%), decrease in
lymphocytes (73%), decrease in leukocytes (71%), increase in mean
corpuscular volume (71%), decrease in absolute neutrophil count
(46%), and decrease in platelets (33%).
ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic
Pancreatic Adenocarcinoma
Most common adverse reactions (Grades 1-4) in ≥10% of patients
who received LYNPARZA in the first-line maintenance setting
for POLO were: fatigue (60%), nausea (45%), abdominal pain
(34%), diarrhea (29%), anemia (27%), decreased appetite (25%),
constipation (23%), vomiting (20%), back pain (19%), arthralgia
(15%), rash (15%), thrombocytopenia (14%), dyspnea (13%),
neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and
stomatitis (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA in the first-line maintenance
setting for POLO were: increase in serum creatinine
(99%), decrease in hemoglobin (86%), increase in mean corpuscular
volume (71%), decrease in lymphocytes (61%), decrease in platelets
(56%), decrease in leukocytes (50%), and decrease in absolute
neutrophil count (25%).
ADVERSE REACTIONS—HRR Gene-mutated Metastatic
Castration-Resistant Prostate Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients
who received LYNPARZA for PROfound were: anemia (46%),
fatigue (including asthenia) (41%), nausea (41%), decreased
appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia
(12%), cough (11%), and dyspnea (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of
patients who received LYNPARZA for PROfound were: decrease
in hemoglobin (98%), decrease in lymphocytes (62%), decrease in
leukocytes (53%), and decrease in absolute neutrophil count
(34%).
ADVERSE REACTIONS—Metastatic Castration-Resistant Prostate
Cancer in Combination with Abiraterone and Prednisone or
Prednisolone
Most common adverse reactions (Grades 1-4) in ≥10% of patients
who received LYNPARZA/abiraterone with a difference of ≥5% compared
to placebo for PROpel were: anemia (48%), fatigue (including
asthenia) (38%), nausea (30%), diarrhea (19%), decreased appetite
(16%), lymphopenia (14%), dizziness (14%), and abdominal pain
(13%).
Most common laboratory abnormalities (Grades 1-4) in ≥20% of
patients who received LYNPARZA/abiraterone for PROpel were:
decrease in hemoglobin (97%), decrease in lymphocytes (70%),
decrease in platelets (23%), and decrease in absolute neutrophil
count (23%).
DRUG INTERACTIONS
Anticancer Agents: Clinical studies of LYNPARZA with
other myelosuppressive anticancer agents, including DNA-damaging
agents, indicate a potentiation and prolongation of
myelosuppressive toxicity.
CYP3A Inhibitors: Avoid coadministration of strong or
moderate CYP3A inhibitors when using LYNPARZA. If a strong or
moderate CYP3A inhibitor must be coadministered, reduce the dose of
LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice,
Seville oranges, and Seville orange juice during LYNPARZA
treatment.
CYP3A Inducers: Avoid coadministration of strong or
moderate CYP3A inducers when using LYNPARZA.
USE IN SPECIFIC POPULATIONS
Lactation: No data are available regarding the presence
of olaparib in human milk, its effects on the breastfed infant or
on milk production. Because of the potential for serious adverse
reactions in the breastfed infant, advise a lactating woman not to
breastfeed during treatment with LYNPARZA and for 1 month after
receiving the final dose.
Pediatric Use: The safety and efficacy of LYNPARZA have
not been established in pediatric patients.
Hepatic Impairment: No adjustment to the starting dose is
required in patients with mild or moderate hepatic impairment
(Child-Pugh classification A and B). There are no data in patients
with severe hepatic impairment (Child-Pugh classification C).
Renal Impairment: No dosage modification is recommended
in patients with mild renal impairment (CLcr 51-80 mL/min estimated
by Cockcroft-Gault). In patients with moderate renal impairment
(CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice
daily. There are no data in patients with severe renal impairment
or end-stage renal disease (CLcr ≤30 mL/min).
INDICATIONS
LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor
indicated:
First-Line Maintenance BRCAm Advanced Ovarian Cancer
For the maintenance treatment of adult patients with deleterious
or suspected deleterious germline or somatic BRCA-mutated (gBRCAm
or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary
peritoneal cancer who are in complete or partial response to
first-line platinum-based chemotherapy. Select patients for therapy
based on an FDA-approved companion diagnostic for LYNPARZA.
First-Line Maintenance HRD-Positive Advanced Ovarian Cancer
in Combination with Bevacizumab
In combination with bevacizumab for the maintenance treatment of
adult patients with advanced epithelial ovarian, fallopian tube or
primary peritoneal cancer who are in complete or partial response
to first-line platinum-based chemotherapy and whose cancer is
associated with homologous recombination deficiency (HRD)-positive
status defined by either:
- a deleterious or suspected deleterious BRCA mutation,
and/or
- genomic instability
Select patients for therapy based on an FDA-approved companion
diagnostic for LYNPARZA.
Maintenance BRCA-mutated Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with deleterious
or suspected deleterious germline or somatic BRCA-mutated (gBRCAm
or sBRCAm) recurrent epithelial ovarian, fallopian tube, or primary
peritoneal cancer, who are in complete or partial response to
platinum-based chemotherapy. Select patients for therapy based on
an FDA-approved companion diagnostic for LYNPARZA.
Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early
Breast Cancer
For the adjuvant treatment of adult patients with deleterious or
suspected deleterious gBRCAm, human epidermal growth factor
receptor 2 (HER2)-negative, high-risk early breast cancer who have
been treated with neoadjuvant or adjuvant chemotherapy. Select
patients for therapy based on an FDA-approved companion diagnostic
for LYNPARZA.
gBRCAm, HER2-Negative Metastatic Breast Cancer
For the treatment of adult patients with deleterious or
suspected deleterious gBRCAm, human epidermal growth factor
receptor 2 (HER2)-negative metastatic breast cancer who have been
treated with chemotherapy in the neoadjuvant, adjuvant, or
metastatic setting. Patients with hormone receptor (HR)-positive
breast cancer should have been treated with a prior endocrine
therapy or be considered inappropriate for endocrine therapy.
Select patients for therapy based on an FDA-approved companion
diagnostic for LYNPARZA.
First-Line Maintenance gBRCAm Metastatic Pancreatic
Cancer
For the maintenance treatment of adult patients with deleterious
or suspected deleterious gBRCAm metastatic pancreatic
adenocarcinoma whose disease has not progressed on at least 16
weeks of a first-line platinum-based chemotherapy regimen. Select
patients for therapy based on an FDA-approved companion diagnostic
for LYNPARZA.
HRR Gene-mutated Metastatic Castration-Resistant Prostate
Cancer
For the treatment of adult patients with deleterious or
suspected deleterious germline or somatic homologous recombination
repair (HRR) gene-mutated metastatic castration-resistant prostate
cancer (mCRPC) who have progressed following prior treatment with
enzalutamide or abiraterone. Select patients for therapy based on
an FDA-approved companion diagnostic for LYNPARZA.
BRCAm Metastatic Castration-Resistant Prostate Cancer in
Combination with Abiraterone and Prednisone or Prednisolone
In combination with abiraterone and prednisone or prednisolone
(abi/pred) for the treatment of adult patients with deleterious or
suspected deleterious BRCA-mutated (BRCAm) metastatic
castration-resistant prostate cancer (mCRPC). Select patients for
therapy based on an FDA-approved companion diagnostic for
LYNPARZA.
Please see complete Prescribing Information,
including Medication Guide.
Notes
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the
ambition to provide cures for cancer in every form, following the
science to understand cancer and all its complexities to discover,
develop and deliver life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers.
It is through persistent innovation that AstraZeneca has built one
of the most diverse portfolios and pipelines in the industry, with
the potential to catalyze changes in the practice of medicine and
transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day,
eliminate cancer as a cause of death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines in Oncology, Rare Diseases and
BioPharmaceuticals, including Cardiovascular, Renal &
Metabolism, and Respiratory & Immunology. Based in Cambridge,
UK, AstraZeneca operates in over 125 countries, and its innovative
medicines are used by millions of patients worldwide. For more
information, please visit www.astrazeneca-us.com and follow us on
social media @AstraZeneca.
US-93392 Last Updated 9/24
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