Results will further underscore efficacy and
safety of IMFINZI®, TAGRISSO®, and LYNPARZA®
across multiple cancers with high unmet need
ENHERTU data will reinforce its
transformative potential in HER2-targetable cancers
New data for MEDI5752 will advance the
science of next-generation immunotherapy
AstraZeneca will present new data supporting its ambition to
redefine cancer care at the European Society for Medical Oncology
(ESMO) Congress 2022, September 9 – 13, 2022.
A total of 15 approved and potential new medicines from
AstraZeneca will be featured across more than 75 abstracts in 13
tumor types.
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, AstraZeneca, said: “At ESMO this year, new evidence will
demonstrate how our medicines are prolonging patient survival
across several cancers. Data from the SOLO-1 and PAOLA-1 Phase III
trials will reinforce the long-term survival benefits of PARP
inhibition with LYNPARZA in advanced ovarian cancer, and new data
for IMFINZI combinations in liver, biliary tract and lung cancers
will show the potential to improve outcomes for patients in these
areas of high unmet need.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “The momentum will continue for ENHERTU at ESMO
with new data across tumor types, including results from the
DESTINY-Lung02 Phase II trial in HER2-mutant metastatic non-small
cell lung cancer which formed the basis for the recent FDA
approval. Additionally, we’re excited to advance the science of
CTLA-4 inhibition with new analyzes presented from two Phase III
trials of IMFINZI plus tremelimumab, HIMALAYA in liver cancer and
POSEIDON in lung cancer, and for MEDI5752, our bispecific antibody
targeting both PD-1 and CTLA-4 in lung cancer.”
Transforming outcomes across tumors over time
Mature disease-free survival (DFS) data from the ADAURA Phase
III trial will be featured in a late-breaking presentation
detailing two years of additional follow-up in patients with
early-stage (Stage IB-IIIA) EGFR-mutated non-small cell lung cancer
(NSCLC) treated with adjuvant TAGRISSO (osimertinib). TAGRISSO is
the only targeted treatment option approved in this setting. The
presentation will also report updated results for patterns of
recurrence and central nervous system DFS.
A late-breaking presentation will feature landmark five-year
overall survival (OS) data from the externally sponsored PAOLA-1
Phase III trial of LYNPARZA (olaparib) in combination with
bevacizumab in 1st-line advanced ovarian cancer, including patients
with homologous recombination deficiency (HRD) positive disease.
This is the longest follow up for a PARP inhibitor in combination
with standard-of-care in this setting.
In addition, seven-year OS data from the SOLO1 Phase III trial
of LYNPARZA for 1st-line maintenance therapy in BRCA-mutated
(BRCAm) advanced ovarian cancer will be presented. This is the
longest follow-up for any PARP inhibitor in newly diagnosed
advanced ovarian cancer.
Data will also include updated OS results at two years from the
TOPAZ-1 Phase III trial of IMFINZI (durvalumab) plus
standard-of-care chemotherapy (gemcitabine plus cisplatin) in
1st-line unresectable or advanced biliary tract cancer, as well as
an analysis of immune-mediated adverse events. TOPAZ-1 is the first
Phase III trial to show improved OS with an immunotherapy
combination versus chemotherapy alone in this setting.
Extending the benefit of antibody drug conjugates (ADCs) to
more patients
Several presentations will demonstrate the clinical potential of
ENHERTU (trastuzumab deruxtecan) treatment across HER2-targetable
lung, gastric and breast cancers.
A late-breaking presentation will feature interim results from
the DESTINY-Lung02 Phase II trial investigating ENHERTU in patients
with HER2-mutant (HER2m) metastatic NSCLC (mNSCLC) who have
progressed following one or more systemic therapies. ENHERTU was
recently approved in the US in this setting as the first
HER2-directed treatment for these patients. Detailed data will also
be shared from the DESTINY-Lung01 Phase II trial, both in this
setting and in patients with HER2-overexpressing mNSCLC.
Another presentation will feature updated data from the
DESTINY-Gastric02 Phase II trial in HER2-positive metastatic
gastric cancer, the first ENHERTU trial in Western patients with
gastric cancer.
Data will also include a subgroup analysis of the
DESTINY-Breast03 Phase III trial of ENHERTU by disease history and
prior treatments in patients with HER2-positive metastatic breast
cancer previously treated with trastuzumab and a taxane.
Patient-reported outcomes from the DESTINY-Breast04 Phase III trial
will also highlight quality of life data for patients treated with
ENHERTU in HER2-low unresectable and/or metastatic breast cancer.
ENHERTU was recently approved in the US as the first HER2-directed
therapy for patients with HER2-low metastatic breast cancer based
on this trial.
Additional posters will describe trials evaluating the
TROP2-directed ADC datopotamab deruxtecan in patients with
hormone-receptor positive, HER2-negative breast cancer
(TROPION-Breast01 Phase III trial) and in a platform trial in
combination with TAGRISSO in patients with advanced NSCLC who have
experienced disease progression (ORCHARD Phase II trial). There are
currently no approved TROP2-directed therapies for patients in
these settings.
Advancing the science of CTLA-4 inhibition
A new analysis from the positive HIMALAYA Phase III trial will
show the impact of viral aetiology on outcomes in unresectable
liver cancer for patients treated with a single priming dose of
tremelimumab, an anti-CTLA-4 antibody, added to IMFINZI (STRIDE
regimen).
In addition, a poster will describe the EMERALD-3 Phase III
trial evaluating tremelimumab added to IMFINZI and transarterial
chemoembolization with or without lenvatinib in unresectable liver
cancer patients eligible for embolisation.
A late-breaking presentation of the positive POSEIDON Phase III
trial in mNSCLC will feature four-year OS outcomes in patients
treated with a limited course of tremelimumab added to IMFINZI plus
chemotherapy.
Another late-breaking presentation will share initial data for
MEDI5752 plus chemotherapy in patients with treatment-naïve Stage
IIIB-IV non-squamous NSCLC. MEDI5752 is a novel bispecific antibody
that simultaneously targets the immune checkpoint proteins PD-1 and
CTLA-4. Bispecific antibodies are a promising approach in
immuno-oncology that combines the potential benefits of two
medicines into one antibody without the increased toxicity seen
with administration of two separate medicines.
Reinforcing the robust benefits of PARP inhibitors across a
broad range of tumor types
In addition to data from PAOLA-1 and SOLO1, an oral presentation
will share updated efficacy analyses across biomarker subgroups
from the PROpel Phase III trial of LYNPARZA plus abiraterone in
patients with newly diagnosed metastatic castration-resistant
prostate cancer (mCRPC) treated with the combination with or
without homologous recombination repair (HRR) gene mutations.
LYNPARZA is the first PARP inhibitor to demonstrate a significant
improvement in radiographic progression-free survival in
combination with abiraterone versus abiraterone alone in 1st-line
mCRPC irrespective of biomarker status.
Additionally, final OS data will be presented from the MEDIOLA
Phase II trial of LYNPARZA and IMFINZI in germline BRCAm
platinum-sensitive relapsed ovarian cancer and from the OPINION
Phase IIIB trial of LYNPARZA maintenance monotherapy in patients
with platinum-sensitive relapsed ovarian cancer without a germline
BRCA1/BRCA2 mutation.
Data will also include an extended OS analysis from the POLO
Phase III trial of LYNPARZA in germline BRCA-mutated metastatic
pancreatic cancer, a disease in which no other PARP inhibitor is
approved.
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 to develop and
commercialize LYNPARZA.
Key AstraZeneca presentations during ESMO 2022
Lead author
Abstract title
Presentation details
Antibody drug conjugates
Goto, K
Trastuzumab Deruxtecan (T-DXd) in Patients
(Pts) With HER2-Mutant Metastatic Non-Small Cell Lung Cancer
(NSCLC): Interim Results From the Phase 2 DESTINY-Lung02 Trial
Presentation #LBA55 Mini Oral Session 11
September 2022 10:15am (CEST)
Ueno, NT
Patient-Reported Outcomes (PROs) From
DESTINY-Breast04, a Randomized Phase 3 Study of Trastuzumab
Deruxtecan (T-DXd) vs Treatment of Physician’s Choice (TPC) in
Patients (pts) With HER2-Low Metastatic Breast Cancer (MBC)
Presentation #217O Proffered Paper Session
11 September 2022 9:30am (CEST)
Ku, GY
Updated Analysis of DESTINY-Gastric02: a
Phase 2 Single-Arm Trial of Trastuzumab Deruxtecan (T-DXd) in
Western Patients (Pts) With HER2-Positive (HER2+)
Unresectable/Metastatic Gastric/Gastroesophageal Junction (GEJ)
Cancer Who Progressed on or After Trastuzumab-Containing
Regimen
Presentation #1205MO Mini Oral Session 10
September 2022 3:45pm (CEST)
Cortés, J
Subgroup Analysis by Disease History and
Prior Treatments of Patients (pts) With HER2-Positive (HER2+)
Metastatic Breast Cancer (MBC) From DESTINY-Breast03, a Randomized
Phase 3 Study of Trastuzumab Deruxtecan (T-DXd) vs Trastuzumab
Emtansine (T-DM1)
Presentation #236P e-Poster 10 September
2022
Li, BT
Phase 2 Trial of Trastuzumab Deruxtecan
(T-DXd) in Patients (Pts) With HER2-Mutated (HER2m) Metastatic
Non-Small Cell Lung Cancer (NSCLC): Registrational Data From
DESTINY-Lung01
Presentation #976P e-Poster 12 September
2022
Bardia, A
Datopotamab deruxtecan (Dato-DXd), a TROP2
antibody-drug conjugate, vs investigators’ choice of chemotherapy
(ICC) in previously-treated, inoperable or metastatic
hormone-receptor (HR) positive, HER2-negative (HR+/HER2–) breast
cancer: TROPION-Breast01
Presentation #274TiP Trial in Progress 10
September 2022
De Langen, J
ORCHARD platform study: osimertinib +
datopotamab deruxtecan (Dato-DXd) cohort in patients (pts) with
advanced NSCLC (aNSCLC) who have progressed on first-line (1L)
osimertinib
Presentation #1188TiP Trial in Progress 12
September 2022
Immuno-oncology
Johnson, ML.
Durvalumab (D) ± tremelimumab (T) +
chemotherapy (CT) in 1L metastatic (m) NSCLC: overall survival (OS)
update from POSEIDON after median follow-up (mFU) of approximately
4 years (y)
Presentation #LBA59 Mini Oral Session 11
September 2022 11:05am (CEST)
Ahn, MJ
MEDI5752 or pembrolizumab (P) plus
carboplatin/pemetrexed (CP) in treatment-naïve (1L) non-small cell
lung cancer (NSCLC): a Phase 1b/2 trial
Presentation #LBA56 Mini Oral Session 11
September 2022 10:20am (CEST)
Spicer, J
Platform study of neoadjuvant durvalumab
(D) alone or combined with novel agents in patients (pts) with
resectable, early-stage non-small-cell lung cancer (NSCLC):
pharmacodynamic correlates and circulating tumor DNA (ctDNA)
dynamics in the NeoCOAST study
Presentation #929MO
Mini Oral Session 12 September 2022 3:15pm
(CEST)
Oh, DY
Updated overall survival (OS) from the
Phase 3 TOPAZ-1 study of durvalumab (D) or placebo (PBO) plus
gemcitabine and cisplatin (+ GC) in patients (pts) with advanced
biliary tract cancer (BTC)
Presentation #56P e-Poster 12 September
2022
Antonuzzo, L
Immune-mediated adverse event (imAE)
incidence, timing and association with efficacy in the Phase 3
TOPAZ-1 study of durvalumab (D) or placebo (PBO) plus gemcitabine
and cisplatin (+ GC) in advanced biliary tract cancer (BTC)
Presentation #57P e-Poster
12 September 2022
Chan, LS
Impact of viral aetiology in the Phase 3
HIMALAYA study of tremelimumab (T) plus durvalumab (D) in
unresectable hepatocellular carcinoma (uHCC)
Presentation #714P e-Poster
12 September 2022
Özgüroğlu, M
Phase 3 trial of durvalumab combined with
domvanalimab following concurrent chemoradiotherapy (cCRT) in
patients with unresectable stage III NSCLC (PACIFIC-8)
Presentation #971TiP Trial in Progress
10 September 2022
Abou-Alfa, GK
A randomized Phase 3 study of tremelimumab
(T) plus durvalumab (D) with or without lenvatinib combined with
concurrent transarterial chemoembolization (TACE) versus TACE alone
in patients (pts) with locoregional hepatocellular carcinoma (HCC):
EMERALD-3
Presentation #727TiP Trial in Progress 12
September 2022
DNA damage response
Ray-Coquard, IL
Final overall survival (OS) results from
the Phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance
olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly
diagnosed advanced ovarian cancer (AOC)
Presentation #LBA29 Proffered Paper
Session 9 September 2022 2:00pm (CEST)
DiSilvestro, P
Overall survival (OS) at 7-year (y)
follow-up (f/u) in patients (pts) with newly diagnosed advanced
ovarian cancer (OC) and a BRCA mutation (BRCAm) who received
maintenance olaparib in the SOLO1/GOG-3004 trial
Presentation #517O Proffered Paper Session
9 September 2022 2:10pm (CEST)
Guo, C
A Phase (Ph) I/II trial of the CXCR2
antagonist AZD5069 in combination with enzalutamide (ENZA) in
patients (pts) with metastatic castration resistant prostate cancer
(mCRPC)
Presentation #454O Proffered Paper Session
10 September 2022 11:15am (CEST)
Saad, F
Biomarker analysis and updated results
from the Phase III PROpel trial of abiraterone (abi) and olaparib
(ola) vs abi and placebo (pbo) as first-line (1L) therapy for
patients (pts) with metastatic castration-resistant prostate cancer
(mCRPC)
Presentation #1357O Proffered Paper
Session 11 September 2022 9:30am (CEST)
Banerjee, S
Phase II study of olaparib plus durvalumab
with or without bevacizumab (MEDIOLA): final analysis of overall
survival in patients with non-germline BRCA-mutated
platinum-sensitive relapsed ovarian cancer
Presentation #529MO Mini Oral Session 11
September 2022 5:00pm (CEST)
Poveda Velasco, AM
Maintenance olaparib monotherapy in
patients (pts) with platinum-sensitive relapsed ovarian cancer (PSR
OC) without a germline BRCA1/BRCA2 mutation (non-gBRCAm): final
overall survival (OS) results from the OPINION trial
Presentation #531P e-Poster 11 September
2022
Hammel, P
Extended overall survival results from the
POLO study of active maintenance olaparib in patients with
metastatic pancreatic cancer and a germline BRCA mutation
Presentation #1298P e-Poster 12 September
2022
Tumor drivers and resistance
Tsuboi, M
Osimertinib as adjuvant therapy in
patients (pts) with resected EGFR-mutated (EGFRm) stage IB–IIIA
non-small cell lung cancer (NSCLC): updated results from ADAURA
Presentation #LBA47 Proffered Paper
Session 11 September 2022 8:30am (CEST)
Piotrowska, Z
ELIOS: A multicenter, molecular profiling
study of patients (pts) with epidermal growth factor
receptor-mutated (EGFRm) advanced NSCLC treated with first-line
(1L) osimertinib
Presentation #LBA53 Proffered Paper
Session 11 September 2022 3:05pm (CEST)
Nakamura, A
Final results and biomarker analysis of a
randomized phase II study of osimertinib plus bevacizumab versus
osimertinib monotherapy for untreated patients with non-squamous
non-small-cell lung cancer harboring EGFR mutations; WJOG9717L
study
Presentation #982P e-Poster 12 September
2022
U.S. 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 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
- 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. 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
In clinical studies, of the 491 patients with unresectable or
metastatic HER2-positive breast cancer treated with ENHERTU 5.4
mg/kg, ILD occurred in 13% of patients. Fatal outcomes due to ILD
and/or pneumonitis occurred in 1.4% of patients treated with
ENHERTU. Median time to first onset was 5.5 months (range: 1.1 to
20.8).
Locally Advanced or Metastatic Gastric
Cancer
In DESTINY-Gastric01, of the 125 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 21.0).
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. Reduce
dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and
temperature >38.3ºC or a sustained temperature of ≥38ºC for more
than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one
level.
Metastatic Breast Cancer
In clinical studies, of the 491 patients with unresectable or
metastatic HER2-positive breast cancer who received ENHERTU 5.4
mg/kg, a decrease in neutrophil count was reported in 68% of
patients. Eighteen percent had Grade 3 or 4 decrease in neutrophil
count. Median time to first onset of decreased neutrophil count was
22 days (range: 6 to 664). Febrile neutropenia was reported in 1.2%
of patients.
Locally Advanced or Metastatic Gastric
Cancer
In DESTINY-Gastric01, of the 125 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
In the 491 patients with unresectable or metastatic
HER2-positive breast cancer who received ENHERTU 5.4 mg/kg, 13
cases (2.6%) of asymptomatic LVEF decrease were reported.
Locally Advanced or Metastatic Gastric
Cancer
In DESTINY-Gastric01, of the 125 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 at least 7
months following the last dose of ENHERTU. Advise male patients
with female partners of reproductive potential to use effective
contraception during treatment with ENHERTU and for at least 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. Reduce dose by
one level.
Adverse Reactions
Metastatic Breast Cancer
The pooled safety population for patients with metastatic breast
cancer reflects exposure to ENHERTU at 5.4 mg/kg given as an
intravenous infusion once every 3 weeks (21-day cycle) in 491
patients in DESTINY-Breast03, DESTINY-Breast01, and Study
DS8201-A-J101. The median duration of treatment was 13 months
(range: 0.7 to 37). In this pooled safety population, the most
common (≥20%) adverse reactions, including laboratory
abnormalities, were nausea (78%), decreased white blood cell count
(74%), decreased hemoglobin (68%), decreased neutrophil count
(68%), increased aspartate aminotransferase (58%), fatigue (57%),
decreased lymphocyte count (56%), vomiting (50%), decreased
platelet count (49%), increased alanine aminotransferase (48%),
increased blood alkaline phosphatase (45%), alopecia (41%),
constipation (35%), hypokalemia (33%), decreased appetite (32%),
diarrhea (31%), musculoskeletal pain (28%), increased transaminases
(27%), respiratory infection (24%), headache (21%), and abdominal
pain (21%).
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 in DESTINY-Breast03. ENHERTU
was administered by intravenous infusion once every three weeks.
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%).
Locally Advanced or Metastatic Gastric
Cancer
The safety of ENHERTU was evaluated in 187 patients with locally
advanced or metastatic HER2positive gastric or GEJ adenocarcinoma
in DESTINYGastric01. Patients intravenously received at least one
dose of either ENHERTU (N=125) 6.4 mg/kg once every three 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) in the ENHERTU group and 2.8 months
(range: 0.5 to 13.1) in the irinotecan/paclitaxel group.
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 following 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 at least 7
months following the last dose. Males: Advise male patients with
female partners of reproductive potential to use effective
contraception during treatment with ENHERTU and for at least 4
months following 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 491 patients with HER2-positive
breast cancer treated with ENHERTU 5.4 mg/kg, 22% were ≥65 years
and 4% 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 (49%). 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 or severe renal
impairment.
- Hepatic Impairment: In patients with moderate hepatic
impairment, due to potentially increased exposure, closely monitor
for increased toxicities related to the topoisomerase
inhibitor.
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.
SELECT SAFETY INFORMATION FOR CALQUENCE®
(acalabrutinib)
INDICATION AND USAGE
CALQUENCE is indicated for the treatment of adult patients with
chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma
(SLL).
SELECT SAFETY INFORMATION
Serious adverse events, including fatal events, have occurred
with CALQUENCE, including serious and opportunistic infections,
hemorrhage, cytopenias, second primary malignancies, and atrial
fibrillation and flutter. The most common adverse reactions (≥ 30%)
of any grade in patients with CLL were anemia, neutropenia,
thrombocytopenia, headache, upper respiratory tract infection, and
diarrhea.
Please see full Prescribing Information
including Patient Information.
SELECT SAFETY INFORMATION FOR IMFINZI® (durvalumab)
Immune-mediated adverse reactions, which may be severe or fatal,
can occur in any organ system or tissue, including the following:
immune-mediated pneumonitis, immune-mediated colitis,
immune-mediated hepatitis, immune-mediated endocrinopathies,
immune-mediated dermatologic adverse reactions, immune-mediated
nephritis and renal dysfunction, and solid organ transplant
rejection. IMFINZI can cause severe or life-threatening
infusion-related reactions. 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/PD-L1 blocking antibody.
Advise women not to become pregnant or breastfeed during
treatment with IMFINZI and for at least 3 months after the last
dose.
In the PACIFIC trial, the most frequent serious adverse
reactions reported in at least 2% of patients were pneumonitis or
radiation pneumonitis (7%) and pneumonia (6%). In the CASPIAN
trial, 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%).
Most common adverse reactions (≥20% of patients with
unresectable, Stage III NSCLC) were cough, fatigue,
pneumonitis/radiation pneumonitis, upper respiratory tract
infections, dyspnea, and rash. Most common adverse reactions (≥20%
of patients with extensive-stage SCLC) were, nausea,
fatigue/asthenia, alopecia.
The safety and effectiveness of IMFINZI have not been
established in pediatric patients.
INDICATION
IMFINZI is indicated for the treatment of patients with
unresectable Stage III non-small cell lung cancer (NSCLC) whose
disease has not progressed following concurrent platinum-based
chemotherapy and radiation therapy.
Please see complete Prescribing Information,
including Patient Information
SELECT SAFETY INFORMATION for LYNPARZA® (olaparib)
tablets
LYNPARZA is associated with serious, potentially fatal risks,
including myelodysplastic syndrome/acute myeloid leukemia
(MDS/AML), pneumonitis. Additionally, serious, potentially fatal
risk of venous thromboembolic events has been reported with
LYNPARZA in mCRPC. LYNPARZA can also cause fetal harm.
U.S. FDA-APPROVED 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 Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with recurrent
epithelial ovarian, fallopian tube, or primary peritoneal cancer,
who are in complete or partial response to platinum-based
chemotherapy.
Advanced gBRCAm Ovarian Cancer
For the treatment of adult patients with deleterious or
suspected deleterious germline BRCA-mutated (gBRCAm) advanced
ovarian cancer who have been treated with 3 or more prior lines of
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.
Please click here for complete Prescribing
Information, including Patient Information (Medication
Guide).
SELECT SAFETY INFORMATION FOR TAGRISSO® (osimertinib)
- There are no contraindications for TAGRISSO
- TAGRISSO is associated with several serious and sometimes fatal
adverse reactions, including interstitial lung disease/pneumonitis,
QTc interval prolongation, cardiomyopathy, keratitis, erythema
multiforme and Stevens-Johnson syndrome, and embryo-fetal
toxicity
- The most common adverse reactions (≥20%) were diarrhea, rash,
dry skin, nail toxicity, stomatitis, fatigue, and decreased
appetite
U.S. FDA-APPROVED INDICATIONS
- TAGRISSO is indicated for the first-line treatment of 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 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.
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 commercialisation of
prescription medicines in Oncology, Rare Diseases, and
BioPharmaceuticals, including Cardiovascular, Renal &
Metabolism, and Respiratory & Immunology. Based in Cambridge,
UK, AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. Please visit
astrazeneca.com and follow the Company on Twitter @AstraZeneca.
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