Aug. 24, 2022 11:00 UTC
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
WILMINGTON, Del.--(BUSINESS WIRE)-- 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.
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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
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