AstraZeneca Aims to Redefine Breast Cancer Care With New Data Across the Treatment Spectrum At SABCS 2022
Data will show clinical opportunity in HR-positive advanced breast cancer for potential first-in-class AKT inhibitor capivasertib and next-generation oral SERD camizestrant
ENHERTU® (fam-trastuzumab deruxtecan-nxki) data will reinforce potential to set new standards in HER2-targetable disease
Data for antibody drug conjugate datopotamab deruxtecan will demonstrate potential in HR-positive and triple-negative breast cancer
WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca will present new data advancing its ambition to redefine care at the 2022 San Antonio Breast Cancer Symposium (SABCS), December 6-10, 2022.
Twelve AstraZeneca medicines and potential new medicines will be featured in 55 presentations, including five oral presentations, showcasing the Company’s growing leadership across different subtypes and stages of breast cancer.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Our data at SABCS are strong validation of our clinical strategy to provide next-generation treatment solutions for patients with nearly all major types of breast cancer. We are excited to share results from the pivotal CAPItello-291 trial, which will support the opportunity of our novel AKT inhibitor capivasertib for patients with HR-positive disease. We also look forward to presenting defining data from the SERENA-2 Phase II trial that will demonstrate the potential of our next-generation SERD camizestrant to improve upon currently available endocrine therapies for patients with ER-driven disease.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “As we close another year of breakthroughs in breast cancer, our presence at SABCS will showcase the opportunity for our portfolio to shape clinical practice and redefine care across subtypes and stages of this disease. Compelling results for potential new medicines capivasertib and camizestrant as well as new data from antibody drug conjugates ENHERTU® (fam-trastuzumab deruxtecan-nxki) and datopotamab deruxtecan will underscore our focus on addressing the greatest unmet needs and delivering personalized treatment for more patients with breast cancer.”
Aiming to set new standards of care across HER2-positive metastatic breast cancer
Two late-breaking presentations from the DESTINY-Breast clinical program will highlight the efficacy of ENHERTU treatment in patients with HER2-positive metastatic breast cancer across lines of therapy.
Updated results from the DESTINY-Breast03 Phase III trial of ENHERTU versus trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer previously treated with trastuzumab and a taxane will be presented, including updated progression-free survival (PFS) data and overall survival (OS) results.
In addition, primary results from the DESTINY-Breast02 Phase III trial will be presented, further demonstrating the clinical benefit of ENHERTU compared to conventional chemotherapy-based regimens in patients with HER2-positive metastatic breast cancer previously treated with T-DM1.
Data will also be presented from the ROSET-BM retrospective study and DEBBRAH Phase II trial further confirming ENHERTU activity in patients with HER2-positive or HER2-low metastatic breast cancer with active or stable brain metastases.
Reshaping treatment expectations in HR-positive advanced breast cancer
A late-breaking presentation will illustrate the Company’s focus on addressing endocrine resistance in advanced HR-positive breast cancer.
Detailed data will be shared from the CAPItello-291 Phase III trial of the AKT inhibitor capivasertib in combination with FASLODEX® (fulvestrant) versus FASLODEX alone in endocrine-resistant, HR-positive, HER2-low or negative advanced breast cancer. CAPItello-291 recently met both primary endpoints, demonstrating improvement in PFS in the overall patient population and in a prespecified biomarker subgroup of patients whose tumors had qualifying alterations in the PIK3CA, AKT1 or PTEN genes.
Several presentations will establish the clinical potential of the next-generation oral selective estrogen receptor degrader (SERD) camizestrant as a monotherapy or in combination for patients with estrogen receptor positive (ER-positive) advanced breast cancer.
- A late-breaking presentation will highlight detailed results from the positive SERENA-2 Phase II trial of camizestrant versus FASLODEX in advanced ER-positive breast cancer.
- Analyses from further cohorts of the SERENA-1 Phase I trial of advanced ER-positive breast cancer will also be presented, which will show the potential to combine camizestrant with abemaciclib, a CDK4/6 inhibitor.
- A spotlight poster will feature data showing promising preclinical activity with camizestrant in ER-positive breast cancer when used in double and triple combinations with CDK4/6, mTOR, AKT or PI3K inhibitors, in ESR1 wild-type and mutated models.
Additionally, several presentations will showcase AstraZeneca’s commitment to transforming the treatment landscape for HR-positive breast cancer with antibody drug conjugates (ADCs) and by identifying new tumor subtypes that may respond to targeted therapies.
- A poster presentation of results from the TROPION-PanTumor01 Phase I trial will characterize the safety and encouraging clinical activity of datopotamab deruxtecan in patients with heavily pre-treated HR-positive, HER2-negative inoperable or metastatic breast cancer. Datopotamab deruxtecan is also being tested in these patients in earlier lines of treatment in the randomized TROPION-Breast01 Phase III trial.
- Multiple poster presentations will share results for potential diagnostic tools to better identify and optimize treatment for patients across the spectrum of HER2 expression, including those with HER2-low tumors who may benefit from treatment with ENHERTU.
- Data from various subgroup analyses from the DESTINY-Breast04 Phase III trial will reinforce the clinical meaningfulness of HER2-low as an actionable patient segment in patients with metastatic breast cancer.
Redefining care for triple-negative breast cancer (TNBC)
Two spotlight poster discussions will share results from the BEGONIA Phase Ib/II trial testing IMFINZI® (durvalumab) combinations in advanced or metastatic TNBC, showing the potential to drive improved outcomes with the addition of ADCs.
Additionally, updated results from the TROPION-PanTumor01 Phase I trial of datopotamab deruxtecan monotherapy will show encouraging and durable anti-tumor activity, and a manageable safety profile in heavily pre-treated patients with metastatic TNBC. The TROPION-Breast02 Phase III trial is evaluating datopotamab deruxtecan as 1st-line therapy for patients with metastatic TNBC.
ENHERTU and datopotamab deruxtecan are developed and commercialized in collaboration with Daiichi Sankyo worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights.
Key AstraZeneca presentations during SABCS 2022
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Lead author |
Abstract title |
Presentation details |
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HER2-positive breast cancer |
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Krop, I |
Trastuzumab deruxtecan vs physician’s choice in patients with HER2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: primary results of the randomized phase 3 study DESTINY-Breast02 |
Presentation #GS2-01 Oral Presentation – General Session 2 December 7, 2022 9:00 – 9:15 AM CT 15:00 – 15:15 GMT |
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Hurvitz, SA |
Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated survival results of the randomized, phase 3 study DESTINY-Breast03 |
Presentation #GS2-02 Oral Presentation – General Session 2 December 7, 2022 9:15 – 9:30 AM CT 15:15 – 15:30 GMT
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Takashi, Y |
Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: A multicenter retrospective study (ROSET-BM study) |
Presentation #PD7-01 Spotlight Poster Discussion 7 December 7, 2022 17:00 CT 23:00 GMT
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Hamilton, EP |
Dose-expansion study of Trastuzumab Deruxtecan as monotherapy or combined with Pertuzumab in patients With metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer in DESTINY-Breast07 (DB-07) |
Presentation #PD18-11 Spotlight Poster Discussion 18 December 9, 2022 07:00 CT 13:00 GMT
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Varghese, D |
A real-world evidence study of treatment patterns in patients with HER2-positive metastatic breast cancer who have received at least 2-lines of therapy |
Presentation #P1-11-19 Poster Session 1 December 6, 2022 17:00 CT 23:00 GMT
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Lam, C |
Treatment patterns and outcomes among patients with HER2-postive metastatic breast cancer in the United States |
Presentation #P4-03-34 Poster Session 4 December 8, 2022 07:00 CT 13:00 GMT
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Henderson, M |
Adverse events (AEs) in phase III clinical trials of patients with human epidermal growth factor receptor-2 positive (HER2+) breast cancer (BC): a meta-analysis |
Presentation #P4-07-53 Poster Session 4 8 December 2022 07:00 CT 13:00 GMT
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Lin, NU |
Open-label, phase 3b/4 study of trastuzumab deruxtecan (T-DXd) in patients with or without baseline brain metastasis with advanced/metastatic human epidermal growth factor receptor 2–positive breast cancer: DESTINY-Breast12 |
Presentation #OT2-16-02 Ongoing Trials Poster Session 2 December 7, 2022 17:00 CT 23:00 GMT
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HER2-low breast cancer |
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Prat, A |
Determination of HER2-low status in tumors of patients with unresectable and/or metastatic breast cancer in DESTINY-Breast04 |
Presentation #HER2-18 HER2 Low: A Separate Entity Special Poster Session December 7, 2022 09:45 – 11:00 CT 15:45 – 17:00 GMT
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Viale, G |
Retrospective Study to Estimate the Prevalence and Describe the Clinicopathological Characteristics, Treatment Patterns, and Outcomes of HER2-Low Breast Cancer |
Presentation #HER2-15 HER2 Low: A Separate Entity Special Poster Session December 7, 2022 09:45 – 11:00 CT 15:45 – 17:00 GMT |
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Rüschoff, J |
Proficiency assessment of HER2-low breast cancer scoring with the Ventana PATHWAY 4B5 and Dako HercepTest HER2 assays and the impact of pathologist training |
Presentation #HER2-13 HER2 Low: A Separate Entity Special Poster Session December 7, 2022 09:45 – 11:00 CT 15:45 – 17:00 GMT |
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Schmid, P |
Trastuzumab deruxtecan (T-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic hormone receptor-negative (HR−), HER2-low breast cancer: updated results from BEGONIA, a phase 1b/2 study |
Presentation #PD11-08 Spotlight Poster Discussion 11 December 8, 2022 07:00 CT 13:00 GMT |
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Pérez-García, JM |
Trastuzumab Deruxtecan in patients with Unstable Central Nervous System Involvement from HER2-Low Advanced Breast Cancer: The DEBBRAH Trial |
Presentation #PD7-02 Spotlight Poster Discussion 7 December 7, 2022 17:00 CT 23:00 GMT
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Harbeck, N |
Trastuzumab deruxtecan vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: Subgroup analyses from DESTINY-Breast04 |
Presentation #P1-11-01 Poster Session 1 December 6, 2022 17:00 CT 23:00 GMT |
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Spitzmüller, A |
Computational pathology based HER2 expression quantification in HER2-low breast cancer |
Presentation #P6-04-03 Poster Session 6 December 9, 2022 07:00 CT 13:00 GMT |
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Tsirka, A |
High Intra- and Inter-block concordance of HER2 immunohistochemistry (IHC) scores across breast cancer samples and impact of decalcification procedures |
Presentation #P6-04-17 Poster Session 6 December 9, 2022 07:00 CT 13:00 GMT |
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Globerson, Y |
A fully automatic artificial intelligence system for accurate and reproducible HER2 IHC scoring in breast cancer |
Presentation #P6-04-05 Poster Session 6 December 9, 2022 07:00 CT 13:00 GMT |
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Kapil, A |
ART: Automated Region segmentation of Tumor on HER2-stained breast cancer tissue |
Presentation #P6-04-16 Poster Session 6 December 9, 2022 07:00 CT 13:00 GMT |
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HR-positive breast cancer |
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Hurvitz, SA |
TRIO-US B-12 TALENT: Neoadjuvant trastuzumab deruxtecan with or without anastrozole for HER2-low, HR+ early stage breast cancer |
Presentation #GS2-03 Oral Presentation – General Session 2 December 7, 2022 09:30 – 09:45 CT 15:30 – 15:45 GMT |
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Oliveira, M |
Camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: Results of the randomized, multi-dose Phase 2 SERENA-2 trial |
Presentation #GS3-02 Oral Presentation – General Session 3 December 8, 2022 08:45 – 09:00 CT 14:45 – 15:00 GMT |
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Turner, NC |
Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: results from the Phase III CAPItello-291 trial |
Presentation #GS3-04 Oral Presentation – General Session 3 December 8, 2022 09:15 – 09:30 CT 15:15 – 15:30 GMT |
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Meric-Bernstam, F |
Phase 1 TROPION-PanTumor01 Study evaluating Datopotamab Deruxtecan (Dato-DXd) in unresectable or metastatic hormone receptor–positive/HER2–negative breast cancer (BC) |
Presentation #PD13-08 Spotlight Poster Discussion 13 December 8, 2022 17:00 CT 23:00 GMT
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Carnevalli, L |
Combination of the next generation oral SERD camizestrant (AZD9833) with CDK4/6 and mTOR/AKT inhibitors delivers robust efficacy in a broad range of ER+ breast tumors |
Presentation #PD10-04 Spotlight Poster Discussion 10 December 8, 2022 07:00 CT 13:00 GMT
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Morrow, C |
The next generation oral selective estrogen receptor degrader (SERD) camizestrant (AZD9833) is active against wild type and mutant estrogen receptor α |
Presentation #P3-07-13 Poster Session 3 December 7, 2022 17:00 CT 23:00 GMT
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Bardia, A |
Datopotamab deruxtecan (Dato-DXd), a TROP2 antibody-drug conjugate,vs investigators’ choice of chemotherapy in previously-treated, inoperable or metastatic HR+/HER2–breast cancer: TROPION-Breast01 |
Presentation #OT1-03-04 Ongoing Trials Poster Session 1 December 6, 2022 17:00 CT 23:00 GMT
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Turner, NC |
SERENA-1: Updated analyses from a Phase 1 study of the next generation oral selective estrogen receptor degrader camizestrant (AZD9833) combined with abemaciclib, in women with ER-positive, HER2-negative advanced breast cancer |
Presentation #OT2-02-01 Ongoing Trials Poster Session 2 December 7, 2022 17:00 CT 23:00 GMT |
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TNBC and BRCA-mutated breast cancer |
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Schmid, P |
Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): updated results from BEGONIA, a phase 1b/2 study |
Presentation #PD11-09 Spotlight Poster Discussion 11 December 8, 2022 07:00 CT 13:00 GMT |
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Bardia, A |
Datopotamab Deruxtecan (Dato-DXd) in advanced triple-negative breast cancer (TNBC): Updated results from the Phase 1 TROPION-PanTumor01 Study |
Presentation #P6-10-03 Poster Session 6 December 9, 2022 07:00 CT 13:00 GMT |
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Copson, ER |
Expert consensus on the definition of high risk of recurrence in HER2-negative eBC: a modified Delphi panel |
Presentation #P3-05-39 Poster Session 3 December 7, 2022 17:00 CT 23:00 GMT |
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Dent, R |
TROPION-Breast02: Phase 3, open-label, randomized study of first-line datopotamab deruxtecan versus chemotherapy in patients with locally recurrent inoperable or metastatic TNBC who are not candidates for anti-PD-(L)1 therapy |
Presentation #OT1-03-05 Ongoing Trials Poster Session 1 December 6, 2022 17:00 CT 23:00 GMT |
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Balmaña, J |
OlympiaN: a phase 2, multicenter, open-label study to assess the efficacy and safety of neoadjuvant olaparib monotherapy and olaparib plus durvalumab in patients with BRCA mutations and early-stage HER2-negative breast cancer |
Presentation #OT2-18-02 Ongoing Trials Poster Session 2 December 7, 2022 17:00 CT 23:00 GMT |
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:
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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
- Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy
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Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy
This indication is approved under accelerated approval based on objective 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 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.
Contacts
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