ENHERTU® (fam-trastuzumab deruxtecan-nxki)
data will show the potential to improve survival for metastatic
breast cancer patients and define a new segment of HER2-low
disease
Results from multiple trials further
reinforce strength of industry-leading portfolio and pipeline,
including novel combinations, across cancers with high unmet
need
AstraZeneca advances its ambition to redefine cancer care with
new data to be presented across its diverse and industry-leading
portfolio of cancer medicines at the American Society of Clinical
Oncology (ASCO) Annual Meeting, June 3-7, 2022.
A total of 18 approved and potential new medicines from
AstraZeneca will be featured across more than 100 abstracts,
including nine oral presentations and a plenary presentation of the
DESTINY-Breast04 Phase III trial for ENHERTU® (fam-trastuzumab
deruxtecan-nxki) in HER2-low metastatic breast cancer.
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, AstraZeneca, said: “Our five leading Oncology medicines have
each set new standards for patient outcomes across many cancers.
Our data at ASCO will showcase our continued investment in driving
innovation with these medicines as well as their long-term impact
in real-world settings. In particular, the groundbreaking data from
DESTINY-Breast04 will show the potential of ENHERTU to treat
patients with HER2-low metastatic breast cancer who have never
before been eligible for HER2-targeted treatments.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “At AstraZeneca, we are pioneering new
biomarkers and novel therapeutic modalities in our ambition to
attack cancer from every angle and deliver personalized medicines
to more patients. The results from DESTINY-Breast04 support the
potential for ENHERTU to redefine the classification and treatment
of breast cancer across the spectrum of HER2 expression. We are
also excited to share promising clinical data for our bispecific
PD1-CTLA4 antibody MEDI5752 in advanced renal cell carcinoma,
designed to have both of these clinically validated checkpoint
targets in one molecule, delivering efficacy with an improved
tolerability profile.”
Leading through disruption in breast cancer
A late-breaking plenary presentation will highlight the
potentially practice-changing results of the DESTINY-Breast04 trial
of ENHERTU in patients with HER2-low metastatic breast cancer.
DESTINY-Breast04 is the first-ever Phase III trial of a
HER2-directed therapy to show statistically significant and
clinically meaningful benefit in both progression-free survival
(PFS) and overall survival (OS) in patients with HER2-low
unresectable and/or metastatic breast cancer regardless of hormone
receptor status compared to standard-of-care chemotherapy.
Additionally, data from a retrospective study will estimate the
prevalence of HER2-low breast cancer and describe its clinical and
pathological characteristics, to help identify patients with
HER2-low expressing tumors who may benefit from HER2-targeted
therapy.
Further results will be shared from dose-finding and
dose-expansion studies of ENHERTU in combination with other
anti-cancer agents in patients with advanced or metastatic
HER2-positive breast cancer (DESTINY-Breast07) and HER2-low breast
cancer (DESTINY-Breast08).
Data will also be presented from a safety follow-up of the
DESTINY-Breast03 Phase III trial of ENHERTU in the treatment of
patients with unresectable or metastatic HER2-positive breast
cancer previously treated with trastuzumab and a taxane. ENHERTU
was recently approved in the US for patients in this setting.
Revealing the full potential of an industry-leading portfolio
and pipeline
Beyond breast cancer, AstraZeneca will share results from
multiple trials highlighting its focus on delivering life-changing
cancer medicines for patients with high unmet need. Data will also
support the Company’s commitment to realizing the full potential of
its leading medicines with ongoing analyses, real-world data and
research into novel combinations.
- MEDI5752 – An oral presentation will share safety and
clinical activity results for MEDI5752 in patients with advanced
renal cell carcinoma as a monotherapy treatment. MEDI5752 is a
novel bispecific antibody that simultaneously targets the immune
checkpoint proteins PD-1 and CTLA-4.
- CALQUENCE® (acalabrutinib) – Updated data from
the ELEVATE-TN and ASCEND Phase III trials will highlight long-term
safety and efficacy results of CALQUENCE in patients with chronic
lymphocytic leukemia (CLL) regardless of line of therapy.
Presentations include updated data with approximately five-years of
median follow-up from the ELEVATE-TN trial, which has demonstrated
sustained clinical benefit of CALQUENCE either in combination with
obinutuzumab or as monotherapy compared to obinutuzumab plus
chlorambucil, providing flexibility to tailor treatment for adults
with treatment-naïve CLL. Additionally, updated results from the
ASCEND Phase III trial with approximately four years of median
follow-up will highlight the sustained reduction of disease
progression or death for CALQUENCE compared to idelalisib plus
rituximab or bendamustine plus rituximab in patients with relapsed
or refractory CLL, as well as a maintained safety profile.
- IMFINZI® (durvalumab) – Patient-reported outcomes
from the HIMALAYA trial will highlight quality of life for patients
treated with a single priming dose of tremelimumab added to IMFINZI
in 1st-line unresectable liver cancer (STRIDE regimen). HIMALAYA is
the first Phase III trial to show that a dual immunotherapy regimen
has improved OS versus sorafenib in this setting. Tremelimumab with
IMFINZI was recently accepted under Priority Review in the US by
the Food and Drug Administration (FDA) based on this trial.
Patient-reported outcomes will also be presented from the TOPAZ-1
trial of IMFINZI plus standard-of-care chemotherapy (gemcitabine
plus cisplatin) in 1st-line advanced biliary tract cancer. TOPAZ-1
is the first Phase III trial to show improved survival with an
immunotherapy combination versus chemotherapy alone in this
setting. An additional regional subgroup analysis for the TOPAZ-1
trial will compare efficacy outcomes, including OS, for Asian
patients with other geographies. IMFINZI plus chemotherapy was
recently granted Priority Review in the US by the FDA based on this
trial. Further clinically relevant safety data from the positive
POSEIDON Phase III trial of IMFINZI, tremelimumab and chemotherapy
in 1st-line metastatic non-small cell lung cancer (NSCLC) will also
be presented.
- LYNPARZA® (olaparib) – Data from the PROpel Phase
III trial will further reinforce the safety profile of LYNPARZA
plus abiraterone in the treatment of 1st-line metastatic
castration-resistant prostate cancer (mCRPC). These data build on
PROpel efficacy data, which demonstrated that this combination
significantly delayed disease progression versus standard-of-care
abiraterone in 1st-line mCRPC in patients with or without
homologous recombination repair gene mutations. LYNPARZA is the
first PARP inhibitor to demonstrate clinical benefit in combination
with a new hormonal agent versus abiraterone alone in this
setting.
- TAGRISSO® (osimertinib) – Results will be shared
from the externally sponsored OPAL Phase II trial in previously
untreated EGFR-mutated (EGFRm) NSCLC that evaluated whether the
addition of platinum-based chemotherapy to TAGRISSO can improve
patient outcomes. This combination is also being tested in the
ongoing FLAURA2 Phase III trial. Real-world data will also be
presented to better inform unmet needs and treatment strategies
among patients with resectable early-stage NSCLC, providing
valuable insights into EGFRm disease prevalence and rates of
recurrence, despite adjuvant chemotherapy, in this population.
TAGRISSO is approved for the adjuvant treatment of early-stage (IB,
II and IIIA) EGFRm NSCLC based on the ADAURA Phase III trial.
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 Merck & Co., Inc., Kenilworth, NJ, US (known as MSD outside
the US and Canada) to develop and commercialize LYNPARZA.
Key AstraZeneca presentations during ASCO 2022
Lead author
Abstract title
Presentation details
Antibody drug conjugates
Modi, S
Trastuzumab deruxtecan (T-DXd) versus
treatment of physician’s choice (TPC) in patients (pts) with
HER2-low unresectable and/or metastatic breast cancer (mBC):
Results of DESTINY-Breast04, a randomized, phase 3 study.
Abstract #LBA3
Plenary Session
June 5, 2022
2:17pm (CDT)
Hamilton, EP
Trastuzumab deruxtecan (T-DXd) versus
trastuzumab emtansine (T-DM1) in patients (pts) with HER2-positive
(HER2+) unresectable and/or metastatic breast cancer (mBC): Safety
follow-up of the randomized, phase 3 study DESTINY-Breast03.
Abstract #1000
Oral Abstract Session Breast
Cancer—Metastatic
June 4, 2022
1:15pm (CDT)
Andre, F
Dose-finding and -expansion studies of
trastuzumab deruxtecan in combination with other anti-cancer agents
in patients (pts) with advanced/metastatic HER2+ (DESTINY-Breast07
[DB-07]) and HER2-low (DESTINY-Breast08 [DB-08]) breast cancer
(BC).
Abstract #3025
Poster Session Developmental
Therapeutics—Molecularly Targeted Agents and Tumor Biology
June 5, 2022
8:00am (CDT)
Immuno-Oncology
Cho, BC
Durvalumab (D) +/- tremelimumab (T) +
chemotherapy (CT) in first-line (1L) metastatic (m) NSCLC: AE
management in POSEIDON.
Abstract #9035
Poster Session Lung Cancer—Non-Small Cell
Metastatic
June 6, 2022
8:00am (CDT)
Sangro, B
Patient-reported outcomes from the phase 3
HIMALAYA study of tremelimumab plus durvalumab in unresectable
hepatocellular carcinoma.
Abstract #4074
Poster Session Gastrointestinal
Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
June 4, 2022
8:00am (CDT)
Burris III, HA
Patient-reported outcomes for the phase 3
TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in
advanced biliary tract cancer.
Abstract #4070
Poster Session Gastrointestinal
Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
June 4, 2022
8:00am (CDT)
Vogel, A
Regional subgroup analysis of the phase 3
TOPAZ-1 study of durvalumab (D) plus gemcitabine and cisplatin (GC)
in advanced biliary tract cancer (BTC).
Abstract #4075
Poster Session Gastrointestinal
Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
June 4, 2022
8:00am (CDT)
Özgüroğlu, M
Adverse events self-reported by patients
(pts) with extensive-stage small cell lung cancer (ES-SCLC) treated
with durvalumab (D) plus platinum-etoposide (EP) or EP in the
CASPIAN study.
Abstract #8571
Poster Session Lung Cancer—Non-Small Cell
Local-Regional/Small Cell/Other Thoracic Cancers
June 6, 2022
8:00am (CDT)
Albiges, L
Safety and clinical activity of MEDI5752,
a PD-1/CTLA-4 bispecific checkpoint inhibitor, as monotherapy in
patients (pts) with advanced renal cell carcinoma (RCC):
Preliminary results from an FTIH trial.
Abstract #107
Clinical Science Symposium Bispecifics:
Are Two Better Than One?
June 5, 2022
10:33am (CDT)
DNA damage response
Pignata, S
Maintenance olaparib in patients (pts)
with platinum-sensitive relapsed ovarian cancer (PSROC) by somatic
(s) or germline (g) BRCA and other homologous recombination repair
(HRR) gene mutation status: Overall survival (OS) results from the
ORZORA study.
Abstract #5519
Poster Discussion Session Gynecologic
Cancer
June 4, 2022
4:30pm (CDT)
Thiery-Vuillemin, A
Tolerability of abiraterone (abi) combined
with olaparib (ola) in patients (pts) with metastatic
castration-resistant prostate cancer (mCRPC): Further results from
the phase III PROpel trial.
Abstract #5019
Poster Discussion Session Genitourinary
Cancer—Prostate, Testicular, and Penile
June 6, 2022
5:26pm (CDT)
Armstrong, AJ
Olaparib plus abiraterone as first-line
therapy in men with metastatic castration-resistant prostate
cancer: Pharmacokinetics data from the PROpel trial.
Abstract #5050
Poster Session Genitourinary
Cancer—Prostate, Testicular, and Penile
June 6, 2022
1:15pm (CDT)
Eskander, RN
Real-world effectiveness of first-line
maintenance olaparib in women with BRCA-mutated advanced ovarian
cancer: U.S. retrospective cohort study.
Abstract #5518
Poster Discussion Session Gynecologic
Cancer
June 4, 2022
4:30pm (CDT)
Tumor drivers and resistance
Jones, RH
Fulvestrant plus capivasertib versus
fulvestrant plus placebo after relapse or progression on an
aromatase inhibitor in metastatic, estrogen receptor–positive
breast cancer (FAKTION): Overall survival and updated
progression-free survival data with enhanced biomarker
analysis.
Abstract #1005
Oral Abstract Session Breast
Cancer—Metastatic
June 4, 2022
2:39pm (CDT)
Nakamura, A
A phase II study of osimertinib in
combination with platinum plus pemetrexed in patients with
EGFR-mutated, advanced non–small cell lung cancer: The OPAL study
(NEJ032C/LOGIK1801).
Abstract #9097
Poster Session Lung Cancer—Non-Small Cell
Metastatic
June 6, 2022
8:00am (CDT)
Hematology
Sharman, JP
Acalabrutinib ± obinutuzumab versus
obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic
leukemia: Five-year follow-up of ELEVATE-TN.
Abstract #7539
Poster Session Hematologic
Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
June 4, 2022
8:00am (CDT)
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
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 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 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 commercialization of prescription medicines in
Oncology, Rare Diseases, and BioPharmaceuticals, including
Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca-us.com and follow the
Company on Twitter @AstraZenecaUS.
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Media Inquiries Brendan McEvoy +1 302 885 2677 Jessica
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