Data to showcase unprecedented efficacy for
TAGRISSO® in early-stage lung cancer and survival results
for IMFINZI® in small cell lung cancer
Further data will highlight the
transformative potential of ENHERTU® across multiple HER2-driven
tumors and new data for IMFINZI plus tremelimumab in liver cancer
and for LYNPARZA® in ovarian cancer
AstraZeneca will present ground-breaking new results across its
broad portfolio of cancer medicines during the 2020 American
Society of Clinical Oncology ASCO20 Virtual Scientific Program, May
29 to May 31, 2020. AstraZeneca will present 98 abstracts,
including 19 oral presentations with one plenary and 10
late-breakers.
Presentations will showcase the Company’s leadership in the
treatment of early lung cancer with a late-breaking plenary
presentation of the unprecedented results from the Phase III ADAURA
trial for TAGRISSO® (osimertinib) in the adjuvant treatment
of patients with Stage IB, II and IIIA epidermal growth factor
receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). Data
from the DESTINY program will highlight the transformative
potential of ENHERTU® (trastuzumab deruxtecan) across
HER2-driven tumors, including in lung, breast, gastric and
colorectal cancers.
José Baselga, Executive Vice President, Oncology R&D, said:
“AstraZeneca continues to deliver results with the goal of
transforming clinical practice. Our science at ASCO this year shows
the potential for treatment of early-stage EGFR-mutated lung
cancer, where we aim to provide the hope of cure with TAGRISSO; to
rewrite the rules on the treatment of patients with HER2-positive
tumors with ENHERTU across a range of cancer settings; and to
advance our next wave of pipeline medicines focused on treating
patients earlier and overcoming resistance.”
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, said: “One constant throughout these uncertain times is our
unwavering commitment to changing the practice of medicine for
patients living with cancer. Our new oncology medicines TAGRISSO,
IMFINZI, LYNPARZA, and ENHERTU are demonstrating incredible
momentum at ASCO, building on their established benefits for
patients by delivering powerful data in new settings and bending
cancer survival curves. This year’s data at ASCO reinforce our
belief that we can one day eliminate cancer as a cause of
death.”
Leadership in lung cancer across stages of disease
As AstraZeneca continues to advance lung cancer research and
development from early to late-stage settings, the Company will
present new data for TAGRISSO, IMFINZI® (durvalumab), ENHERTU, and
potential new medicine savolitinib. Beyond ADAURA, an oral
presentation of the final analysis of the Phase III CASPIAN trial
confirms the sustained, clinically meaningful overall survival (OS)
benefit of IMFINZI for patients with extensive-stage small cell
lung cancer (ES-SCLC). Another oral presentation reinforces the
potential of ENHERTU for patients with HER2-mutant NSCLC (see
below). Results from a Phase II trial of savolitinib in patients
with mesenchymal-epithelial transition (MET) exon 14 skipping
mutations will also be presented.
Transforming treatment across HER2-driven cancers
AstraZeneca, in collaboration with Daiichi Sankyo Company,
Limited (Daiichi Sankyo) will present new data from several trials
highlighting the transformative potential of ENHERTU, including
detailed results from the Phase II DESTINY-Gastric01 trial which
showed a statistically significant and clinically meaningful
improvement in objective response rate and OS for patients with
HER2-positive metastatic gastric cancer. ENHERTU was recently
granted Breakthrough Therapy Designation in the US for patients in
this setting. Phase II data will also be presented for
HER2-positive colorectal cancer and HER2-mutant NSCLC, two cancer
settings for which there are currently no approved HER2-targeted
medicines. Additionally, subgroup analyses from the Phase II
DESTINY-Breast01 trial will reinforce the durable and consistent
responses seen with ENHERTU in HER2-positive metastatic breast
cancer.
Advancing treatment in other cancer types with high unmet
need
AstraZeneca will present data from several trials highlighting
how the Company’s leading research is progressing treatment in
other cancers where a high unmet medical need remains,
including:
- An oral presentation of results from Study 22 for the IMFINZI
plus tremelimumab combination using a novel regimen in advanced
liver cancer
- Final OS results from the Phase III SOLO2 trial for
LYNPARZA® (olaparib) maintenance treatment in patients with
BRCA-mutated platinum-sensitive relapsed ovarian cancer in an oral
presentation. LYNPARZA is developed and commercialized in
collaboration with Merck & Co., Inc. (Merck: known as MSD
outside the US and Canada)
- Multiple trials underscoring the impressive profile of
CALQUENCE®(acalabrutinib), including data from the Phase II
ACE-CL-001 trial with more than four years of follow up. The
presentations represent the most mature safety and efficacy data to
date with CALQUENCE monotherapy in patients with chronic
lymphocytic leukemia
Key AstraZeneca presentations during the ASCO20 Virtual
Scientific Program
Lead author
Abstract title
Presentation
details1
Immuno-Oncology
Paz-Ares, L
Durvalumab ± tremelimumab +
platinum-etoposide in first-line ES-SCLC: Results from the Phase
III CASPIAN study
Abstract #9002
Oral Abstract Session - Lung Cancer -
Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Chen, Y
First-line durvalumab plus
platinum-etoposide in ES-SCLC (CASPIAN): Impact of brain metastases
on treatment patterns and outcomes
Abstract #9068
Poster #261
Poster Session - Lung Cancer - Non-Small
Cell Local-Regional/Small Cell/Other Thoracic Cancers
Naidoo, J
Non-pneumonitis immune-mediated adverse
events with durvalumab in patients with unresectable, Stage III
NSCLC (PACIFIC)
Abstract #9048
Poster #241
Poster Session - Lung Cancer - Non-Small
Cell Local-Regional/Small Cell/Other Thoracic Cancers
Kelley, RK
Efficacy, tolerability, and biologic
activity of a novel regimen of tremelimumab in combination with
durvalumab for patients with advanced hepatocellular carcinoma
(Study 22)
Abstract #4508
Oral Abstract Session - Gastrointestinal
Cancer - Gastroesophageal, Pancreatic, and Hepatobiliary
Oh, Do-Youn
Phase II study assessing tolerability,
efficacy and biomarkers for durvalumab ± tremelimumab and
gemcitabine/cisplatin in chemo-naïve advanced biliary tract
cancer
Abstract #4520 Poster #128
Poster Session - Gastrointestinal Cancer:
Gastroesophageal, Pancreatic, and Hepatobiliary
Lim, E
A Phase I, open-label multi-center study
to assess the safety, pharmacokinetics, and the preliminary
antitumor activity of AZD4635 both as monotherapy and in
combination in patients with advanced solid malignancies: results
from prostate cancer patients
Abstract #5518 Poster #99
Poster Session - Genitourinary Cancer -
Prostate, Testicular, and Penile
DNA damage response
Poveda, A
Final overall survival results from SOLO2:
a Phase III trial assessing maintenance olaparib in patients with
platinum-sensitive, relapsed ovarian cancer and a BRCA mutation
Abstract #6002
Oral Abstract Session - Gynecologic
Cancer
Cadoo, K
Olaparib treatment in patients with
platinum-sensitive relapsed ovarian cancer by BRCA mutation and
homologous recombination deficiency status: Phase II LIGHT
study
Abstract #6013 Poster #184
Poster Discussion - Gynecologic Cancer
Lee, J
Cediranib in combination with olaparib in
patients without a germline BRCA1/2 mutation with recurrent
platinum-resistant ovarian cancer: Phase IIb CONCERTO trial
Abstract #6056 Poster #227
Poster Session - Gynecologic Cancer
Poveda, A
Olaparib maintenance monotherapy for
non-germline BRCA1/2-mutated platinum-sensitive relapsed ovarian
cancer patients: Phase IIIb OPINION interim analysis
Abstract #6057 Poster #228
Poster Session - Gynecologic Cancer
Liu, J
A Phase III study comparing single-agent
olaparib or the combination of cediranib and olaparib to standard
platinum-based chemotherapy in recurrent platinum-sensitive ovarian
cancer
Abstract #6003
Oral Abstract Session - Gynecologic
Cancer
Gelmon, K
Real-world clinical effectiveness and
safety of olaparib monotherapy in HER2-negative gBRCA-mutated
metastatic breast cancer: Phase IIIb LUCY interim analysis
Abstract #1087
Poster #172
Poster Session - Breast Cancer -
Metastatic
Tumor drivers and resistance
Herbst, R
Osimertinib as adjuvant therapy in
patients with Stage IB–IIIA EGFRm NSCLC after complete tumor
resection: ADAURA
Abstract #LBA5
Plenary Session Sunday 31 May, 1:00pm
EDT
Lu, S
Phase II study of savolitinib in patients
with pulmonary sarcomatoid carcinoma and other types of NSCLC
harboring MET exon 14 skipping mutations
Abstract #9519
Poster #285
Poster Discussion - Lung Cancer -
Non-Small Cell Metastatic
Choueiri, T
SAVOIR: A Phase III study of savolitinib
vs. sunitinib in patients with MET-driven papillary renal cell
carcinoma
Abstract #5002
Oral Abstract Session - Genitourinary
Cancer - Kidney and Bladder
Julia, K
Concurrent osimertinib plus gefitinib for
first-line treatment of EGFR-mutated NSCLC
Abstract # 9507
Oral Abstract Session - Lung Cancer-
Non-Small Cell Metastatic
Piotrowska, Z
ECOG-ACRIN 5162: A Phase II study of
osimertinib 160 mg in NSCLC with EGFR exon 20 insertions
Abstract #9513
Poster #279
Poster Discussion - Lung Cancer -
Non-Small Cell Metastatic
Hamilton, E
A Phase I dose escalation and expansion
study of the next generation oral SERD AZD9833 in women with
ER-positive, HER2-negative advanced breast cancer (SERENA-1)
Abstract #1024
Poster #109
Poster Discussion - Breast Cancer -
Metastatic
Schmid, P
A Phase III trial of capivasertib and
paclitaxel in first-line treatment of patients with metastatic
triple-negative breast cancer (CAPItello290)
Abstract #TPS1109
Poster #194
Poster Session - Breast Cancer -
Metastatic
Hematology
Ghia, P
Acalabrutinib vs Idelalisib plus Rituximab
or Bendamustine plus Rituximab in Relapsed/Refractory Chronic
Lymphocytic Leukemia: ASCEND Final Results
Abstract #8015
Poster #348
Poster Discussion - Hematologic
Malignancies - Lymphoma and Chronic Lymphocytic Leukemia
Byrd, C
Acalabrutinib in Treatment-Naïve Chronic
Lymphocytic Leukemia: Mature Results From Phase II Study
Demonstrating Durable Remissions and Long-Term Tolerability
Abstract #8024
Poster #357
Poster Session - Hematologic Malignancies
- Lymphoma and Chronic Lymphocytic Leukemia
Furman, R
Safety of Acalabrutinib Monotherapy in
Hematologic Malignancies: Pooled Analysis From Clinical Trials
Abstract #8064
Poster #397
Poster Session - Hematologic Malignancies
- Lymphoma and Chronic Lymphocytic Leukemia
Antibody drug conjugates
Smit, E
Trastuzumab deruxtecan in patients with
HER2-mutated metastatic NSCLC: Interim results of
DESTINY-Lung01
Abstract # 9504
Oral Abstract Session - Lung Cancer-
Non-Small Cell Metastatic
Shitara, K
Trastuzumab deruxtecan in patients with
HER2-positive advanced gastric or gastroesophageal junction
adenocarcinoma: A randomized, Phase II, multicenter, open-label
study (DESTINY-Gastric01)
Abstract #4513
Poster #121
Poster Session - Gastrointestinal Cancer -
Gastroesophageal, Pancreatic, and Hepatobiliary
Siena, S
A Phase II, multicenter, open-label study
of trastuzumab deruxtecan in patients with HER2-expressing
metastatic colorectal cancer: DESTINY-CRC01
Abstract #4000
Oral Abstract Session - Gastrointestinal
Cancer - Colorectal and Anal
Modi, S
Trastuzumab deruxtecan for HER2-positive
metastatic breast cancer: DESTINY-Breast01 subgroup analysis
Abstract #1036
Poster #121
Poster Session - Breast Cancer-
Metastatic
1. Beginning Friday, May 29 at 8:00 AM EDT oral presentations,
poster discussions and poster sessions will be available on demand
for 180 days including video and slide presentations, as well as
discussant commentary
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
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.
U.S. FDA-Approved Indication for ENHERTU
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 two or more prior anti-HER2-based regimens in the
metastatic setting.
This indication is approved under accelerated approval based on
tumor response rate and duration of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in a confirmatory trial.
WARNING: INTERSTITIAL LUNG DISEASE and
EMBRYO-FETAL TOXICITY
- Interstitial lung disease (ILD) and pneumonitis, including
fatal cases, have been reported with ENHERTU. Monitor for and
promptly investigate signs and symptoms including cough, dyspnea,
fever, and other new or worsening respiratory symptoms. Permanently
discontinue ENHERTU in all patients with Grade 2 or higher
ILD/pneumonitis. Advise patients of the risk and to immediately
report symptoms.
- Exposure to ENHERTU during pregnancy can cause embryo-fetal
harm. Advise patients of these risks and the need for effective
contraception.
Contraindications
None.
WARNINGS AND PRECAUTIONS
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease
(ILD), including pneumonitis, can occur in patients treated with
ENHERTU. In clinical studies, of the 234 patients with unresectable
or metastatic HER2-positive breast cancer treated with ENHERTU, ILD
occurred in 9% of patients. Fatal outcomes due to ILD and/or
pneumonitis occurred in 2.6% of patients treated with ENHERTU.
Median time to first onset was 4.1 months (range: 1.2 to 8.3).
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 prednisolone or
equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater),
permanently discontinue ENHERTU. Promptly initiate corticosteroid
treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg
prednisolone or equivalent). Upon improvement, follow by gradual
taper (e.g., 4 weeks).
Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in
patients treated with ENHERTU. Of the 234 patients with
unresectable or metastatic HER2-positive breast cancer who received
ENHERTU, a decrease in neutrophil count was reported in 30% of
patients and 16% had Grade 3 or 4 events. Median time to first
onset was 1.4 months (range: 0.3 to 18.2). Febrile neutropenia was
reported in 1.7% of patients.
Monitor complete blood counts prior to initiation of ENHERTU and
prior to each dose, and as clinically indicated. Based on the
severity of neutropenia, ENHERTU may require dose interruption or
reduction. 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.
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. In the 234 patients with unresectable
or metastatic HER2-positive breast cancer who received ENHERTU, two
cases (0.9%) of asymptomatic LVEF decrease were reported. 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.
Assess LVEF prior to initiation of ENHERTU and at regular
intervals during treatment as clinically indicated. Manage LVEF
decrease through treatment interruption. Permanently discontinue
ENHERTU if LVEF of <40% or absolute decrease from baseline of
>20% is confirmed. 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.
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.
Adverse Reactions
The safety of ENHERTU was evaluated in a pooled analysis of 234
patients with unresectable or metastatic HER2-positive breast
cancer who received at least one dose of ENHERTU 5.4 mg/kg in
DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered
by intravenous infusion once every three weeks. The median duration
of treatment was 7 months (range: 0.7 to 31).
Serious adverse reactions occurred in 20% of patients receiving
ENHERTU. Serious adverse reactions in >1% of patients who
received ENHERTU were interstitial lung disease, pneumonia,
vomiting, nausea, cellulitis, hypokalemia, and intestinal
obstruction. Fatalities due to adverse reactions occurred in 4.3%
of patients including interstitial lung disease (2.6%), and the
following events occurred in one patient each (0.4%): acute hepatic
failure/acute kidney injury, general physical health deterioration,
pneumonia, and hemorrhagic shock.
ENHERTU was permanently discontinued in 9% of patients, of which
ILD accounted for 6%. Dose interruptions due to adverse reactions
occurred in 33% of patients treated with ENHERTU. The most frequent
adverse reactions (>2%) associated with dose interruption were
neutropenia, anemia, thrombocytopenia, leukopenia, upper
respiratory tract infection, fatigue, nausea, and ILD. Dose
reductions occurred in 18% of patients treated with ENHERTU. The
most frequent adverse reactions (>2%) associated with dose
reduction were fatigue, nausea, and neutropenia.
The most common adverse reactions (frequency ≥20%) were nausea
(79%), fatigue (59%), vomiting (47%), alopecia (46%), constipation
(35%), decreased appetite (32%), anemia (31%), neutropenia (29%),
diarrhea (29%), leukopenia (22%), cough (20%), and thrombocytopenia
(20%).
Use in Specific Populations
- Pregnancy: ENHERTU can cause fetal harm when
administered to a pregnant woman. Advise patients of the potential
risks to a fetus. There are clinical considerations if ENHERTU is
used in pregnant women, or if a patient becomes pregnant within 7
months 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 234 patients with HER2-positive
breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years
and 5% were ≥75 years. No overall differences in efficacy 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 (53%) as compared to
younger patients (42%).
- 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 WARNING, and Medication Guide.
SELECT SAFETY INFORMATION for LYNPARZA® (olaparib)
tablets
LYNPARZA is associated with serious, potentially fatal risks,
including myelodysplastic syndrome/acute myeloid leukemia (MDS/AML)
and pneumonitis. LYNPARZA can also cause fatal harm.
Please see complete Prescribing Information, including
Patient Information.
SELECT SAFETY INFORMATION for IMFINZI® (durvalumab) injection
for intravenous use
- Serious, potentially fatal risks were seen with IMFINZI 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%).
- Immune-mediated adverse reactions including immune-mediated
pneumonitis, hepatitis, colitis, endocrinopathies (including
thyroid disorders, adrenal insufficiency, type 1 diabetes, and
hypophysitis), nephritis, dermatologic reactions, other
immune-mediated adverse reactions, infection, and infusion-related
reactions were reported in patients receiving IMFINZI in the
CASPIAN trial.
- The most common adverse reactions (≥20%) were nausea,
fatigue/asthenia and alopecia.
- Advise women not to become pregnant or breastfeed during
treatment with IMFINZI and for at least 3 months after the last
dose.
- The safety and effectiveness of IMFINZI have not been
established in pediatric patients.
INDICATION
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).
Please see complete Prescribing Information, including
Patient Information.
IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE® (acalabrutinib)
capsules
Serious and Opportunistic Infections
Fatal and serious infections, including opportunistic
infections, have occurred in patients with hematologic malignancies
treated with CALQUENCE.
Serious or Grade 3 or higher infections (bacterial, viral, or
fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in
clinical trials, most often due to respiratory tract infections
(11% of all patients, including pneumonia in 6%). These infections
predominantly occurred in the absence of Grade 3 or 4 neutropenia,
with neutropenic infection reported in 1.9% of all patients.
Opportunistic infections in recipients of CALQUENCE have included,
but are not limited to, hepatitis B virus reactivation, fungal
pneumonia, Pneumocystis jiroveci pneumonia, Epstein-Barr virus
reactivation, cytomegalovirus, and progressive multifocal
leukoencephalopathy (PML). Consider prophylaxis in patients who are
at increased risk for opportunistic infections. Monitor patients
for signs and symptoms of infection and treat promptly.
Hemorrhage
Fatal and serious hemorrhagic events have occurred in patients
with hematologic malignancies treated with CALQUENCE. Major
hemorrhage (serious or Grade 3 or higher bleeding or any central
nervous system bleeding) occurred in 3.0% of patients, with fatal
hemorrhage occurring in 0.1% of 1029 patients exposed to CALQUENCE
in clinical trials. Bleeding events of any grade, excluding
bruising and petechiae, occurred in 22% of patients.
Use of antithrombotic agents concomitantly with CALQUENCE may
further increase the risk of hemorrhage. In clinical trials, major
hemorrhage occurred in 2.7% of patients taking CALQUENCE without
antithrombotic agents and 3.6% of patients taking CALQUENCE with
antithrombotic agents. Consider the risks and benefits of
antithrombotic agents when co-administered with CALQUENCE. Monitor
patients for signs of bleeding.
Consider the benefit-risk of withholding CALQUENCE for 3-7 days
pre- and post-surgery depending upon the type of surgery and the
risk of bleeding.
Cytopenias
Grade 3 or 4 cytopenias, including neutropenia (23%), anemia
(8%), thrombocytopenia (7%), and lymphopenia (7%), developed in
patients with hematologic malignancies treated with CALQUENCE.
Grade 4 neutropenia developed in 12% of patients. Monitor complete
blood counts regularly during treatment. Interrupt treatment,
reduce the dose, or discontinue treatment as warranted.
Second Primary Malignancies
Second primary malignancies, including skin cancers and other
solid tumors, occurred in 12% of 1029 patients exposed to CALQUENCE
in clinical trials. The most frequent second primary malignancy was
skin cancer, reported in 6% of patients. Monitor patients for skin
cancers and advise protection from sun exposure.
Atrial Fibrillation and Flutter
Grade 3 atrial fibrillation or flutter occurred in 1.1% of 1029
patients treated with CALQUENCE, with all grades of atrial
fibrillation or flutter reported in 4.1% of all patients. The risk
may be increased in patients with cardiac risk factors,
hypertension, previous arrhythmias, and acute infection. Monitor
for symptoms of arrhythmia (e.g., palpitations, dizziness, syncope,
dyspnea) and manageas appropriate.
ADVERSE REACTIONS
The most common adverse reactions (≥ 20%) of any grade in
patients with relapsed or refractory MCL were anemia,*
thrombocytopenia,* headache (39%), neutropenia,* diarrhea (31%),
fatigue (28%), myalgia (21%), and bruising (21%). The most common
Grade ≥ 3 non-hematological adverse reaction (reported in at least
2% of patients) was diarrhea (3.2%).
*Treatment-emergent decreases (all grades) of hemoglobin (46%),
platelets (44%), and neutrophils (36%) were based on laboratory
measurements and adverse reactions.
Dose reductions or discontinuations due to any adverse reaction
were reported in 1.6% and 6.5% of patients, respectively. Increases
in creatinine 1.5 to 3 times the upper limit of normal occurred in
4.8% of patients.
The most common adverse reactions (≥ 30%) of any grade in
patients with CLL were anemia,* neutropenia,* thrombocytopenia,*
headache, upper respiratory tract infection, and diarrhea.
*Treatment-emergent decreases (all grades) of hemoglobin,
platelets, and neutrophils were based on laboratory measurements
and adverse reactions.
In patients with previously untreated CLL exposed to CALQUENCE,
fatal adverse reactions that occurred in the absence of disease
progression and with onset within 30 days of the last study
treatment were reported in 2% for each treatment arm, most often
from infection. Serious adverse reactions were reported in 39% of
patients in the CALQUENCE plus obinutuzumab arm and 32% in the
CALQUENCE monotherapy arm, most often due to events of pneumonia
(7% and 2.8%, respectively).
Adverse reactions led to CALQUENCE dose reduction in 7% and 4%
of patients in the CALQUENCE plus obinutuzumab arm (N=178) and
CALQUENCE monotherapy arm (N=179), respectively. Adverse events led
to discontinuation in 11% and 10% of patients, respectively.
Increases in creatinine 1.5 to 3 times the upper limit of normal
occurred in 3.9% and 2.8% of patients in the CALQUENCE combination
arm and monotherapy arm, respectively.
In patients with relapsed/refractory CLL exposed to CALQUENCE,
serious adverse reactions occurred in 29% of patients. Serious
adverse reactions in > 5% of patients who received CALQUENCE
included lower respiratory tract infection (6%). Fatal adverse
reactions within 30 days of the last dose of CALQUENCE occurred in
2.6% of patients, including from second primary malignancies and
infection.
Adverse reactions led to CALQUENCE dose reduction in 3.9% of
patients (N=154), dose interruptions in 34% of patients, most often
due to respiratory tract infections followed by neutropenia, and
discontinuation in 10% of patients, most frequently due to second
primary malignancies followed by infection. Increases in creatinine
1.5 to 3 times the upper limit of normal occurred in 1.3% of
patients who received CALQUENCE.
DRUG INTERACTIONS
Strong CYP3A Inhibitors: Avoid co-administration with a
strong CYP3A inhibitor. If a strong CYP3A inhibitor will be used
short-term, interrupt CALQUENCE.
Moderate CYP3A Inhibitors: When CALQUENCE is
co-administered with a moderate CYP3A inhibitor, reduce CALQUENCE
dose to 100 mg once daily.
Strong CYP3A Inducers: Avoid co-administration with a
strong CYP3A inducer. If a strong CYP3A inducer cannot be avoided,
increase the CALQUENCE dose to 200 mg approximately every 12
hours.
Gastric Acid Reducing Agents: If treatment with a gastric
acid reducing agent is required, consider using an H2-receptor
antagonist or an antacid. Take CALQUENCE 2 hours before taking an
H2-receptor antagonist. Separate dosing with an antacid by at least
2 hours.
Avoid co-administration with proton pump inhibitors. Due to the
long-lasting effect of proton pump inhibitors, separation of doses
may not eliminate the interaction with CALQUENCE.
SPECIFIC POPULATIONS
Based on findings in animals, CALQUENCE may cause fetal harm and
dystocia when administered to a pregnant woman. There are no
available data in pregnant women to inform the drug-associated
risk. Advise pregnant women of the potential risk to a fetus.
Pregnancy testing is recommended for females of reproductive
potential prior to initiating CALQUENCE therapy. Advise female
patients of reproductive potential to use effective contraception
during treatment with CALQUENCE and for at least 1 week following
the last dose of CALQUENCE.
It is not known if CALQUENCE is present in human milk. Advise
lactating women not to breastfeed while taking CALQUENCE and for at
least 2 weeks after the final dose.
Avoid administration of CALQUENCE in patients with severe
hepatic impairment. Dose modifications are not required for
patients with mild or moderate hepatic impairment.
Please see full Prescribing Information including Patient
Information.
About the Collaboration between AstraZeneca and Daiichi
Sankyo
In March 2019, AstraZeneca and Daiichi Sankyo entered into a
global collaboration to jointly develop and commercialize ENHERTU
worldwide, except in Japan where Daiichi Sankyo maintains exclusive
rights. Daiichi Sankyo is solely responsible for manufacturing and
supply.
About the AstraZeneca and Merck Strategic Oncology
Collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth,
NJ, US, known as MSD outside the US and Canada, announced a global
strategic oncology collaboration to co-develop and co-commercialize
LYNPARZA, the world’s first PARP inhibitor, for multiple cancer
types. Working together, the companies will develop LYNPARZA in
combination with other potential new medicines and as
monotherapies. Independently, the companies will develop LYNPARZA
in combination with their respective PD-L1 and PD-1 medicines.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a
quickly growing portfolio of new medicines that has the potential
to transform patients' lives and the Company's future. With six new
medicines launched between 2014 and 2020, and a broad pipeline of
small molecules and biologics in development, the Company is
committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investments that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - and by championing the development
of personalized combinations, AstraZeneca has the vision to
redefine cancer treatment 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, primarily for the treatment of diseases in
three therapy areas - Oncology, Cardiovascular, Renal and
Metabolism, and Respiratory. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of
patients worldwide. Please visit www.astrazeneca-us.com and follow
us on Twitter @AstraZenecaUS.
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