Two highly anticipated Presidential Symposia
for TROPION-Lung01 and TROPION-Breast01 will unveil the
significance of datopotamab deruxtecan in lung and breast
cancers
FLAURA2 data reinforce TAGRISSO®
(osimertinib) as the backbone therapy in EGFR-mutated lung cancer
and underscore its added benefit of treating brain
metastases
DUO-E results for IMFINZI® (durvalumab) plus
LYNPARZA® (olaparib) will show the benefit of immunotherapy and
PARP inhibitor combinations in endometrial cancer for the first
time
First IMFINZI data in gastric cancer from
MATTERHORN Phase III trial will highlight the potential of
immunotherapy combinations in earlier settings and growing
leadership in gastrointestinal cancers
AstraZeneca advances its ambition to eliminate cancer as a cause
of death with new data across its robust portfolio and pipeline at
the European Society for Medical Oncology (ESMO) Congress, October
20-24, 2023.
Nearly 100 abstracts will feature 19 approved and potential new
medicines from AstraZeneca including two late-breaking Presidential
Symposia and 26 oral presentations. Highlights include:
- TROPION-Lung01 Phase III trial of AstraZeneca and
Daiichi Sankyo’s datopotamab deruxtecan (Dato-DXd) in patients with
previously treated advanced non-small cell lung cancer (NSCLC)
(Presidential Symposium, Monday, October 23).
- TROPION-Breast01 Phase III trial of datopotamab
deruxtecan in patients with previously treated inoperable or
metastatic hormone receptor (HR)-positive, HER2-low or negative
breast cancer (Presidential Symposium, Monday, October 23).
- FLAURA2 Phase III trial of TAGRISSO® (osimertinib) plus
chemotherapy in EGFR-mutated (EGFRm) advanced NSCLC including
safety and central nervous system metastases outcomes. Results were
recently presented from the progression-free survival (PFS) primary
analysis.
- DUO-E Phase III trial of IMFINZI® (durvalumab) plus
platinum-based chemotherapy followed by either IMFINZI monotherapy
or IMFINZI plus LYNPARZA® (olaparib) as maintenance therapy in
newly diagnosed advanced or recurrent edometrial cancer.
- MATTERHORN Phase III trial of IMFINZI plus neoadjuvant
chemotherapy (before surgery) for patients with resectable,
early-stage and locally advanced (Stages II, III, IVA) gastric and
gastroesophageal junction (GEJ) cancers.
- DESTINY-PanTumor02 Phase II trial of AstraZeneca and
Daiichi Sankyo’s ENHERTU® (fam-trastuzumab deruxtecan-nxki) in
previously treated HER2-expressing advanced solid tumors including
PFS and overall survival (OS) data from the primary analysis.
- Three bispecifics: data from several presentations will
highlight the Company’s robust clinical program of novel
immuno-oncology (IO) bispecific antibodies including data for
volrustomig in advanced clear cell renal cell carcinoma (MEDI5752,
targeting PD-1/CTLA-4), and data for rilvegostomig (AZD2936,
targeting PD-1/TIGIT) and sabestomig (AZD7789, targeting PD-1/TIM3)
in lung cancer.
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “At ESMO, we are building on the potential of
our antibody drug conjugate portfolio with results from the
TROPION-Lung01 and TROPION-Breast01 Phase III trials demonstrating
the promise of datopotamab deruxtecan for patients across multiple
cancer types in two back-to-back Presidential Symposia. These first
pivotal data from our robust clinical program are just the
beginning for this TROP2-directed antibody drug conjugate, which we
believe could replace conventional chemotherapy for many
patients.”
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, AstraZeneca, said: “Our key data at ESMO demonstrate our
commitment to redefining cancer care across a growing number of
tumor types with high unmet need. Across lung, breast, gynecologic
and gastrointestinal cancers, the first data will be presented from
four different pivotal trials which will raise the bar for patients
with multiple medicines from our industry-leading portfolio and
highlight the power of novel combinations.”
Datopotamab deruxtecan takes center stage with promising data
in lung and breast cancers
A Presidential Symposium will highlight PFS data from the
TROPION-Lung01 Phase III trial evaluating datopotamab deruxtecan in
patients with previously treated advanced NSCLC. In July,
datopotamab deruxtecan became the first antibody drug conjugate to
demonstrate a statistically significant improvement in PFS and a
trend in improvement for OS compared to docetaxel, the current
standard-of-care chemotherapy. Additionally, a mini-oral
presentation will feature initial results from the TROPION-Lung05
Phase II trial evaluating datopotamab deruxtecan in patients with
heavily pretreated advanced NSCLC with actionable genomic mutations
(AGA). There are currently no TROP2-directed antibody drug
conjugates approved for the treatment of patients with lung
cancer.
Another Presidential Symposium will showcase data from the
TROPION-Breast01 Phase III trial of datopotamab deruxtecan in
patients with inoperable or metastatic hormone receptor
(HR)-positive, HER2-low or negative breast cancer previously
treated with endocrine-based therapy and at least one systemic
therapy. In September, datopotamab deruxtecan demonstrated a
statistically significant and clinically meaningful improvement in
PFS and a trend in improvement for OS compared to investigator’s
choice of chemotherapy.
Lastly, a mini-oral presentation will highlight updated safety
and efficacy results from the BEGONIA Phase Ib/II trial of
datopotamab deruxtecan plus IMFINZI in patients with previously
untreated unresectable, locally advanced or metastatic
triple-negative breast cancer (TNBC), including duration of
response. Early data from the trial presented previously
demonstrated promising clinical responses in this setting,
regardless of PD-L1 expression (low and high tumors).
IMFINZI combinations enter new tumor types and continue
delivering in lung and biliary tract cancers
A late-breaking oral presentation will feature PFS data from the
DUO-E Phase III trial evaluating treatment with IMFINZI and
chemotherapy followed by either IMFINZI plus LYNPARZA or IMFINZI
alone as maintenance therapy in patients with newly diagnosed
advanced or recurrent endometrial cancer. High-level results
recently announced showed both regimens demonstrated a
statistically significant and clinically meaningful improvement in
PFS compared to standard-of-care chemotherapy alone, with greater
clinical benefit observed with the combination of IMFINZI and
LYNPARZA as maintenance treatment.
Another late-breaking oral presentation will highlight
pathologic complete response (pCR) data from the MATTERHORN Phase
III trial of IMFINZI added to standard-of-care FLOT (fluorouracil,
leucovorin, oxaliplatin, and docetaxel) neoadjuvant chemotherapy
for patients with resectable, early-stage and locally advanced
gastric and GEJ cancers versus neoadjuvant therapy alone.
High-level interim results demonstrated a statistically significant
and clinically meaningful improvement in the key secondary endpoint
of pCR. This is the first global Phase III trial of an
immunotherapy and FLOT chemotherapy combination to demonstrate
clinical benefit in this setting. The trial is continuing to assess
the primary endpoint of event-free survival.
Also in gastrointestinal cancers, two poster presentations of
new data from the TOPAZ-1 Phase III trial will further reinforce
the benefit of IMFINZI plus chemotherapy as a 1st-line
standard-of-care treatment for advanced biliary tract cancer.
Results will be shared from an exploratory analysis of an extended
cohort of TOPAZ-1 patients enrolled in China. Additionally, results
will be shared from an exploratory analysis assessing the impact of
prognostic or predictive factors of OS in the trial.
A late-breaking mini-oral presentation in lung cancer will
report exploratory analyses from the AEGEAN Phase III trial of
IMFINZI-based treatment before and after surgery in patients with
resectable NSCLC, evaluating potential associations between
circulating tumor DNA (ctDNA) and neoadjuvant treatment
responses.
Extending the benefits of ENHERTU across HER2-expressing
tumors
New data from the DESTINY-PanTumor02 and DESTINY-PanTumor01
Phase II trials will underscore the potential of ENHERTU for
previously treated patients with HER2-expressing or HER2-mutated
advanced solid tumors, respectively, who currently have no targeted
treatment options.
A late-breaking mini-oral presentation of primary results from
DESTINY-PanTumor02 will highlight efficacy and safety outcomes for
ENHERTU in patients with HER2-expressing solid tumors. In July,
high-level primary analysis results showed ENHERTU demonstrated
clinically meaningful PFS and OS, as well as provided robust and
durable tumor responses across multiple HER2-expressing solid
tumors in the trial. Additionally, a poster presentation will share
exploratory biomarker analyses of HER2 expression and gene
amplification in tissue and baseline plasma ctDNA.
A further oral presentation will feature the first report of
primary results from DESTINY-PanTumor01 in patients with solid
tumors that have specific HER2-activating mutations.
A mini-oral presentation will feature post-hoc pooled efficacy
and safety analyses of the DESTINY-Lung01 and DESTINY-Lung02 Phase
II trials of ENHERTU in patients with HER2-mutated metastatic NSCLC
with and without brain metastases.
Several presentations will feature new data from the
DESTINY-Breast clinical program for ENHERTU, including its efficacy
in patients with brain metastases.
Progressing next-wave treatments including best-in-class
bispecifics
Several presentations will share data from AstraZeneca’s
portfolio of novel IO bispecific antibodies, underscoring the
Company’s investment in a robust clinical program for this next
wave of IO therapy. These include:
- A mini-oral presentation of data from a Phase Ib trial of
volrustomig (MEDI5752), a PD-1/CTLA-4 bispecific antibody, in the
1st-line treatment of patients with advanced clear cell renal cell
carcinoma.
- Another mini-oral presentation of safety and preliminary
efficacy results from the Phase I/IIa first-in-human trial of
sabestomig (AZD7789), a PD-1/TIM-3 bispecific antibody, in patients
with Stages IIIb-IV NSCLC resistant to previous anti-PD(L)1
therapy.
- A poster presentation of data from the ARTEMIDE-01 Phase I
trial assessing rilvegostomig (AZD2936), a PD-1/TIGIT bispecific
antibody, in patients with advanced or metastatic NSCLC.
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, and with Merck & Co., Inc., known
as MSD outside the US and Canada, to develop and commercialize
LYNPARZA both as a monotherapy and in combination with other
potential medicines. Independently, the companies are developing
LYNPARZA in combination with their respective PD-L1 and PD-1
medicines, IMFINZI and pembrolizumab, in a number of tumor
types.
Key AstraZeneca presentations during ESMO 2023
Lead
Author
Abstract
Title
Presentation
details (CEST)
Antibody drug conjugates
Datopotamab deruxtecan
Ahn, M (presented by Lisberg,
A)
Datopotamab deruxtecan (Dato-DXd) vs
docetaxel in previously treated advanced/metastatic (adv/met)
non-small cell lung cancer (NSCLC): Results of the randomized phase
3 study TROPION-Lung01
Abstract #LBA12 Presidential 3 October 23,
2023 04:42 PM
Bardia, A
Datopotamab deruxtecan (Dato-DXd) vs
chemotherapy in previously-treated inoperable or metastatic hormone
receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC):
Primary results from the randomized Phase 3 TROPION-Breast01
trial
Abstract #LBA11 Presidential 3 October 23,
2023 04:30 PM
Paz-Ares, L
TROPION-Lung05: Datopotamab deruxtecan
(Dato-DXd) in previously treated non-small cell lung cancer (NSCLC)
with actionable genomic alterations (AGAs)
Abstract #1341MO Mini oral session 1 –
NSCLC, metastatic October 21, 2023 09:30 AM
Schmid, P
Datopotamab deruxtecan (Dato-DXd) +
durvalumab (D) as first-line (1L) treatment for unresectable
locally advanced/metastatic triple-negative breast cancer
(a/mTNBC): updated results from BEGONIA, a phase 1b/2 study
Abstract #379MO Mini oral session – Breast
cancer, metastatic
October 22, 2023 08:30 AM
ENHERTU
Modi, S
Fam-trastuzumab deruxtecan-nxki (T-DXd)
Versus Treatment of Physician’s Choice (TPC) in patients (pts) With
HER2-Low Unresectable and/or Metastatic Breast Cancer (mBC):
Updated Survival Results of the Randomized, Phase 3
DESTINY-Breast04 Study
Abstract #376O Proffered Paper session –
Breast cancer, metastatic October 21, 2023 10:25 AM
Hurvitz, S
A Pooled Analysis of fam-trastuzumab
deruxtecan-nxki (T-DXd) in Patients (pts) With HER2-Positive
(HER2+) Metastatic Breast Cancer (Mbc) With Brain Metastases (BMs)
from DESTINY-Breast (DB) -01, 02, and -03
Abstract #377O
Proffered Paper session – Breast cancer,
metastatic
October 21, 2023
10:55 AM
Li, B
Efficacy and safety of fam-trastuzumab
deruxtecan-nxki (T-DXd) in patients (pts) with solid tumors
harboring specific HER2- activating mutations (HER2m): primary
results from the international phase 2 DESTINY- PanTumor01 (DPT-01)
study
Abstract #654O Proffered Paper session –
Developmental therapeutics October 22, 2023 09:20 AM
Li, B
Fam-trastuzumab deruxtecan-nxki (T-DXd) in
Patients (pts) With HER2 (ERBB2)-Mutant (HER2m) Metastatic
Non–Small Cell Lung Cancer (NSCLC) With and Without Brain
Metastases (BMs): Pooled Analyses From DESTINY-Lung01 and
DESTINY-Lung02
Abstract #1321MO Mini oral session 2 –
NSCLC, metastatic October 22, 2023 0:9:05 AM
Meric-Bernstam, F
Fam-trastuzumab deruxtecan-nxki (T-DXd)
for pretreated patients (pts) with HER2- expressing solid tumors:
primary analysis from the DESTINY-PanTumor02 (DP-02) study
Abstract #LBA34 Mini oral session –
Developmental therapeutics October 23, 2023 04:40 PM
Smit, E
Baseline Circulating Tumor DNA (ctDNA)
Biomarker Analysis of Patients With Human Epidermal Growth Factor
Receptor 2 (HER2)- Overexpressing Metastatic Non–Small Cell Lung
Cancer (NSCLC) Treated With Fam- trastuzumab deruxtecan-nxki
(T-DXd)
Abstract #151P e-Poster – Biomarkers
(agnostic) October 21, 2023
Tsurutani, J
Subgroup Analysis of Patients (pts) With
HER2-Low Metastatic Breast Cancer (mBC) With Brain Metastases (BMs)
at Baseline From DESTINY-Breast04, A Randomized Phase 3 Study of
Fam-trastuzumab deruxtecan-nxki (T-DXd) vs Treatment of Physicians
Choice (TPC)
Abstract #388P
e-Poster – Breast cancer, metastatic
October 21, 2023
AZD5335
Meric-Bernstam, F
FONTANA: A Phase 1/2a study of AZD5335 as
monotherapy and in combination with anti- cancer agents in patients
with solid tumors
Abstract #819TiP e-Poster – Gynecological
cancers October 22, 2023
Immuno-oncology
Westin, S
Durvalumab (durva) plus
carboplatin/paclitaxel (CP) followed by maintenance (mtx) durva ±
olaparib (ola) as a first line (1L) treatment for newly diagnosed
advanced or recurrent endometrial cancer (EC): results from the
Phase III DUO-E/GOG-3041/ENGOT-EN10 trial
Abstract #LBA41 Proffered Paper session 2
– Gynecological cancers October 21, 2023 09:15 AM
Janjigian, Y (presented by
Al-Batran, S)
Pathological complete response to 5-
fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT)
chemotherapy with or without durvalumab in resectable gastric and
gastroesophageal junction cancer (GC/GEJC): Interim results of the
phase 3, randomized, double-blind MATTERHORN study
Abstract #LBA73 Proffered Paper session 1
– Gastrointestinal tumors, upper digestive October 20, 2023 02:10
PM
Garassino, M
Durvalumab (durva) after sequential
chemoradiotherapy (CRT) in patients (pts) with unresectable Stage
III NSCLC: Final analysis from PACIFIC-6
Abstract #LBA61 Mini oral session 2 –
Non-metastatic NSCLC and other thoracic malignancies October 23,
2023 03:20 PM
Reck, M
Associations of ctDNA clearance and
pathological response with neoadjuvant treatment in patients with
resectable NSCLC from the phase 3 AEGEAN trial
Abstract #LBA59 Mini oral session 2 –
Non-metastatic NSCLC and other thoracic malignancies October 23,
2023 03:00 PM
Filippi, A
Durvalumab after radiotherapy (RT) in
patients with unresectable Stage III NSCLC ineligible for
chemotherapy (CT): Primary results from the DUART study
Abstract #LBA62 Mini oral session 2 –
Non-metastatic NSCLC and other thoracic malignancies October 23,
2023 03:30 PM
Besse, B
Safety and preliminary efficacy of
AZD7789, a bispecific antibody targeting PD-1 and TIM-3, in
patients (pts) with stage IIIB-IV non-small cell lung cancer
(NSCLC) with previous anti- PD-L(1) therapy
Abstract #1313MO Mini oral session 1 –
NSCLC, metastatic October 21, 2023 09:15 AM
Voss, M
MEDI5752 (volrustomig), a novel PD-1/CTLA-
4 bispecific antibody, in the first-line (1L) treatment of 65
patients (pts) with advanced clear cell renal carcinoma (aRCC)
Abstract #1883MO Mini oral session –
Genitourinary tumors, non-prostate October 22, 2023 11:25 AM
Brandão, M
Preliminary efficacy and safety of
rilvegostomig (AZD2936), a bispecific antibody targeting PD-1 and
TIGIT, in checkpoint inhibitor (CPI)-pretreated advanced/metastatic
non-small-cell lung cancer (NSCLC): ARTEMIDE-01
Abstract #1446P e-Poster – NSCLC,
metastatic October 23, 2023
He, A
Potentially prognostic factors of overall
survival in advanced biliary tract cancer in the randomized Phase 3
TOPAZ-1 study
Abstract #102P e-Poster – Biliary tract
cancer, incl. cholangiocarcinoma October 23, 2023
Qin, S
Efficacy and safety of durvalumab plus
gemcitabine and cisplatin in Chinese participants with advanced
biliary tract cancer: extension cohort of the Phase 3, randomized,
double-blind, placebo-controlled, global TOPAZ-1 study
Abstract #98P e-Poster – Biliary tract
cancer, incl. cholangiocarcinoma October 23, 2023
Tumor drivers and resistance
Jänne, P
Circulating tumor DNA (ctDNA) profiling in
patients (pts) with EGFR-mutated (EGFRm) advanced NSCLC receiving
osimertinib + chemotherapy vs osimertinib monotherapy: FLAURA2
Abstract #LBA68 Mini oral session 1 –
NSCLC, metastatic October 21, 2023 08:30 AM
DNA damage response
Mehra, N
Efficacy of Olaparib (ola) + abiraterone
(abi) vs placebo (pbo) + abi in the non-BRCA mutation (non-BRCAm)
subgroup of patients (pts) with metastatic castration-resistant
prostate cancer (mCPRC) in the PROpel trial
Abstract #1805P e-Poster – Prostate cancer
October 22, 2023
SELECT SAFETY INFORMATION FOR TAGRISSO® (osimertinib)
- There are no contraindications for TAGRISSO
- Interstitial lung disease (ILD)/pneumonitis occurred in
patients treated with TAGRISSO, some of which were fatal. Withhold
TAGRISSO and promptly investigate for ILD in patients who present
with worsening respiratory symptoms. Permanently discontinue if
confirmed
- Monitor patients who have a history or predisposition for QTc
prolongation or those who are taking medications that are 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 TAGRISSO-treated patients, some of
which were fatal. Monitor patients with cardiac risk factors and
assess left ventricular ejection fraction in patients who develop
symptoms during treatment. Permanently discontinue TAGRISSO in
patients with symptomatic congestive heart failure
- Promptly refer patients with signs and symptoms of keratitis to
an ophthalmologist
- Withhold TAGRISSO if erythema multiforme major, Stevens-Johnson
syndrome or toxic epidermal necrolysis is suspected and permanently
discontinue if confirmed
- 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, including fatal cases, has been reported in
patients treated with TAGRISSO. Inform patients of the signs and
symptoms of aplastic anemia. 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 women prior to use. Advise women to
use effective contraception during treatment with TAGRISSO and for
6 weeks after the final dose. Advise men to use effective
contraception during treatment with TAGRISSO and for 4 months after
the final dose
- Most common (≥20%) adverse reactions, including laboratory
abnormalities, were leukopenia, lymphopenia, thrombocytopenia,
diarrhea, anemia, rash, musculoskeletal pain, nail toxicity,
neutropenia, dry skin, stomatitis, fatigue, and cough
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 for the treatment of adult patients with
metastatic 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 1.5% of patients exposed
to LYNPARZA monotherapy, and the majority of events had a fatal
outcome. The median duration of therapy in patients who developed
MDS/AML was 2 years (range: <6 months to >10 years). All of
these patients had previous chemotherapy with platinum agents
and/or other DNA-damaging agents, including radiotherapy.
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.
IMPORTANT SAFETY INFORMATION FOR IMFINZI® (durvalumab) AND
IMJUDO® (tremelimumab-actl)
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.
- 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.
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
- 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.
- 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.
- 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.
- 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).
- 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 IMJUDO in combination with durvalumab,
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.
The safety and effectiveness of IMFINZI and IMJUDO have not been
established in pediatric patients.
Indications:
IMFINZI 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 IMJUDO and platinum-based
chemotherapy, is indicated for the treatment of adult patients with
metastatic NSCLC with no sensitizing epidermal growth factor
receptor (EGFR) mutations or anaplastic lymphoma kinase (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).
Please see Full Prescribing Information including Medication
Guide for IMFINZI and IMJUDO.
IMPORTANT SAFETY INFORMATION FOR ENHERTU® (fam-trastuzumab
deruxtecan-nxki)
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor
conjugate indicated for the treatment of adult patients with:
- Unresectable or metastatic HER2-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 gastric or
gastroesophageal junction adenocarcinoma who have received a prior
trastuzumab-based regimen
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.
Metastatic Breast Cancer and HER2-Mutant
NSCLC (5.4 mg/kg) In patients with metastatic breast cancer
and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, ILD occurred
in 12% of patients. Fatal outcomes due to ILD and/or pneumonitis
occurred in 1.0% of patients treated with ENHERTU. Median time to
first onset was 5 months (range: 0.9 to 23).
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.
Metastatic Breast Cancer and HER2-Mutant
NSCLC (5.4 mg/kg) In patients with metastatic breast cancer
and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, a decrease in
neutrophil count was reported in 65% of patients. Sixteen percent
had Grade 3 or 4 decreased neutrophil count. Median time to first
onset of decreased neutrophil count was 22 days (range: 2 to 664).
Febrile neutropenia was reported in 1.1% of patients.
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.
Metastatic Breast Cancer and HER2-Mutant
NSCLC (5.4 mg/kg) In patients with metastatic breast cancer
and HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, LVEF decrease
was reported in 3.6% of patients, of which 0.4% were Grade 3.
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 Metastatic Breast
Cancer and HER2-Mutant NSCLC (5.4 mg/kg) The pooled safety
population reflects exposure to ENHERTU 5.4 mg/kg intravenously
every 3 weeks in 984 patients in Study DS8201-A-J101 (NCT02564900),
DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, and
DESTINY-Lung02. Among these patients 65% were exposed for >6
months and 39% were exposed for >1 year. In this pooled safety
population, the most common (≥20%) adverse reactions, including
laboratory abnormalities, were nausea (76%), decreased white blood
cell count (71%), decreased hemoglobin (66%), decreased neutrophil
count (65%), decreased lymphocyte count (55%), fatigue (54%),
decreased platelet count (47%), increased aspartate
aminotransferase (48%), vomiting (44%), increased alanine
aminotransferase (42%), alopecia (39%), increased blood alkaline
phosphatase (39%), constipation (34%), musculoskeletal pain (32%),
decreased appetite (32%), hypokalemia (28%), diarrhea (28%), and
respiratory infection (24%).
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 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%),
hypokalemia (35%), constipation (34%), musculoskeletal pain (31%),
diarrhea (29%), decreased appetite (29%), respiratory infection
(22%), headache (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
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 hypokalemia
(25%).
Unresectable or Metastatic HER2-Mutant
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
unresectable or metastatic HER2-mutant NSCLC who received ENHERTU
5.4 mg/kg intravenously every three weeks 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, hypokalemia, 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%).
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 hypokalemia. 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%), hypokalemia (30%), vomiting (26%), constipation
(24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia
(22%).
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 883 patients with breast cancer
treated with ENHERTU 5.4 mg/kg, 22% were ≥65 years and 3.6% 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 (60%) as compared to
younger patients (48%). Of the 101 patients with unresectable or
metastatic HER2-mutant 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 locally
advanced or metastatic HER2-positive 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.
- 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.
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.
Notes
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the
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the potential to catalyse changes in the practice of medicine and
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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
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