AstraZeneca Reinforces Leadership in Breast Cancer at SABCS 2021 With New Data Underscoring Ambition to Redefine Cancer Care
December 3, 2021Data from DESTINY-Breast03 will reaffirm the efficacy of ENHERTU in treating HER2-positive metastatic breast cancer, including patients with stable brain metastases
Extensive portfolio of nine approved and potential new medicines to be featured across subtypes and stages of disease, including data for novel combinations
WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca will underscore its ambition to redefine care with new data from across its portfolio of innovative medicines at the 2021 San Antonio Breast Cancer Symposium (SABCS) December 7-10, 2021.
Fourteen AstraZeneca medicines and potential new medicines from the pipeline will be featured across 33 abstracts showcasing the Company’s leadership across different types and stages of breast cancer, including three oral presentations.
Breast cancer is now the most diagnosed cancer worldwide with an estimated 2.3 million people diagnosed in 2020.1
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Continuing our year of breakthroughs in breast cancer, our data at SABCS will reinforce the practice-changing potential of ENHERTU with new analyses from the DESTINY-Breast03 trial. Early data from the BEGONIA and TROPION-PanTumor01 trials demonstrate great promise in treating patients who have limited treatment options. These data build on our decades of experience in pioneering medicines to redefine care for patients.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Progress in breast cancer increasingly involves more personalized approaches to treating patients across subtypes and stages of disease, which is a key focus of our data at this year’s SABCS. Our extensive knowledge of breast cancer disease biology and the patient experience fuel our ambition to deliver medicines that can truly revolutionize and reshape treatment for every type of breast cancer patient.”
Transforming the treatment of advanced breast cancers with antibody drug conjugates (ADCs)
An oral presentation will share further results from a range of patient subgroups from the DESTINY-Breast03 Phase III trial, including those with stable brain metastases and patients characterized by hormone receptor status, number of prior lines of therapy or status of visceral metastasis.
Results from DESTINY-Breast03 demonstrated superior progression-free survival (PFS) for ENHERTU® (fam-trastuzumab deruxtecan-nxki) versus trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer previously treated with trastuzumab and a taxane.
In another oral presentation, updated results from the TROPION-PanTumor01 Phase I trial will continue to build promising evidence of the anti-tumor activity of datopotamab deruxtecan in patients with triple-negative breast cancer (TNBC).
Treating breast cancer early where there is more opportunity for cure
New data on patient quality of life from the OlympiA Phase III trial of LYNPARZA® (olaparib) will be presented as an oral presentation.
These patient-reported outcomes data will provide compelling evidence that further supports LYNPARZA as a potential treatment option for the adjuvant treatment of patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.
The supplemental New Drug Application of LYNPARZA for this indication was recently granted Priority Review by the US Food and Drug Administration.
Changing the treatment landscape with next-generation medicines and novel combinations
A poster and spotlight poster discussion will share results from the BEGONIA Phase Ib/II trial testing IMFINZI® (durvalumab) combinations in advanced/metastatic TNBC with data from arm 1 (IMFINZI plus paclitaxel), arm 2 (IMFINZI, paclitaxel and capivasertib) and arm 5 (IMFINZI, paclitaxel and oleclumab), which will further demonstrate the benefits of combining immune checkpoint inhibitors with other novel molecules.
Additionally, ongoing trials posters will share information about the ongoing SERENA-4 Phase III trial which evaluates our next-generation oral selective estrogen receptor degrader (SERD) camizestrant (AZD9833) in combination with CDK4/6 inhibitors in the 1st-line treatment of patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, and the SERENA-6 Phase III trial of camizestrant with CDK4/6 inhibitors in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer with an ESR1 mutation.
A further ongoing trial poster will share information on the CAPItello-292 Phase III trial, evaluating the benefit of adding capivasertib (an AKT inhibitor) to the treatment regimen of FASLODEX® (fulvestrant) and palbociclib in patients with HR-positive, HER2-negative locally advanced, unresectable or metastatic breast cancer.
ENHERTU and datopotamab deruxtecan are developed and commercialized in collaboration with Daiichi Sankyo worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights. LYNPARZA is developed and commercialized in collaboration with Merck & Co., Inc., known as MSD outside the US and Canada.
Key AstraZeneca presentations during SABCS 2021
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Lead author |
Abstract title |
Presentation details |
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ENHERTU (fam-trastuzumab deruxtecan-nxki) |
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Hurvitz S |
Trastuzumab deruxtecan (T-DXd; DS-8201a) vs. trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer (mBC): results of the randomized phase 3 study DESTINY-Breast03 |
Presentation GS3-01 Oral – General Session 3 December 9, 2021 08:45 – 11:30 CT 14:45 – 17:30 GMT |
|
Vaz Batista M |
Trastuzumab deruxtecan in patients with HER2[+] or HER2-low–expressing advanced breast cancer and central nervous system involvement: Preliminary results from the DEBBRAH phase 2 study [IIS] |
Publication PD4-06 Spotlight Poster Discussion 4 December 8, 2021 17:00 – 18:30 CT 23:00 – 00:30 (+1) GMT |
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Datopotamab deruxtecan (Dato-DXd) |
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Krop I |
Datopotamab deruxtecan (Dato-DXd) in Advanced/Metastatic Human Epidermal Growth Factor Receptor 2 Negative (HER2−) Breast Cancer: Results From the Phase 1 TROPION-PanTumor01 Study [J101 TNBC prelim results] |
Presentation GS1-05 Oral presentation – General Session 1 December 7, 2021 08:00 – 10:45 CT 14:00 – 16:45 GMT |
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LYNPARZA (olaparib) |
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Ganz PA |
Quality of life results from OlympiA: A phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)-adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high risk HER-2 negative early breast cancer |
Presentation GS4-09 Oral – General Session 4 December 10, 2021 08:45 – 11:15 CT 14:45 – 17:15 GMT |
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IMFINZI (durvalumab) |
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Schmid P |
BEGONIA: Phase 1b/2 study of durvalumab (d) combinations in locally advanced/metastatic triple-negative breast cancer (TNBC): Results from arm 1 d + paclitaxel (p), arm 2 d + p + capivasertib (c), and arm 5 d + p + oleclumab (o) |
Publication PD10-03 Spotlight Poster Discussion 10 December 9, 2021 17:00 – 18:30 CT 23:00 – 00:30 (+1) GMT |
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Camizestrant (AZD9833) |
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André F |
SERENA-4: A Phase III comparison of AZD9833 (camizestrant) plus palbociclib, versus anastrozole plus palbociclib, for patients with ER-positive/HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease |
Publication OT2-11-06 Ongoing Trials Poster Session 2 December 9, 2021 17:00 – 18:30 CT 23:00 – 00:30 (+1) GMT |
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Bidard FC |
SERENA-6: A Phase III study to assess the efficacy and safety of AZD9833 (camizestrant) compared with aromatase inhibitors when given in combination with palbociclib or abemaciclib in patients with HR+/HER2- metastatic breast cancer with detectable ESR1m who have not experienced disease progression on first-line therapy |
Publication OT2-11-05 Ongoing Trials Poster Session 2 December 9, 2021 17:00 – 18:30 CT 23:00 – 00:30 (+1) GMT |
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FASLODEX (fulvestrant) and capivasertib |
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Rugo HS |
CAPItello-292: A phase Ib/III study of capivasertib, palbociclib and fulvestrant, versus placebo, palbociclib and fulvestrant, for endocrine therapy-resistant HR+/HER2− advanced breast cancer |
Publication OT2-14-01 Ongoing Trials Poster Session 2 December 9, 2021 17:00 – 18:30 CT 23:00 – 00:30 (+1) GMT |
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.
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 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%).
The most common adverse reactions were cough, fatigue, pneumonitis or radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash.
The safety and effectiveness of IMFINZI have not been established in pediatric patients.
Please click here for complete Prescribing Information, including Patient Information.
IMPORTANT SAFETY INFORMATION FOR ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:
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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.
- Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
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WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY |
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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 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 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).
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 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 62% of patients. Sixteen percent had Grade 3 or 4 decrease in neutrophil count. Median time to first onset of decreased neutrophil count was 23 days (range: 6 to 547). Febrile neutropenia was reported in 1.7% 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. 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. 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. 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. 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.
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 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 (≥20%) adverse reactions, including laboratory abnormalities, were nausea (79%), white blood cell count decreased (70%), hemoglobin decreased (70%), neutrophil count decreased (62%), fatigue (59%), vomiting (47%), alopecia (46%), aspartate aminotransferase increased (41%), alanine aminotransferase increased (38%), platelet count decreased (37%), constipation (35%), decreased appetite (32%), anemia (31%), diarrhea (29%), hypokalemia (26%), and cough (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.
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