Atezolizumab + Trastuzumab Emtansine for Breast Cancer
(Astefania Trial)
Recruiting in Palo Alto (17 mi)
+403 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Hoffmann-La Roche
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a Phase III, two-arm, randomized, double-blind placebo-controlled study in participants with HER2-positive primary breast cancer who have received preoperative chemotherapy and HER2-directed therapy, including trastuzumab followed by surgery, with a finding of residual invasive disease in the breast and/or axillary lymph nodes.
As of June 4, 2024, this study is no longer accepting any newly screened participants.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop your current medications. However, if you are on immunostimulatory or immunosuppressive agents, you may need to stop them, as these are part of the exclusion criteria.
What data supports the idea that Atezolizumab + Trastuzumab Emtansine for Breast Cancer is an effective drug?
The available research shows that Trastuzumab Emtansine (T-DM1) is effective for treating HER2-positive metastatic breast cancer. It has demonstrated better results and fewer side effects compared to standard treatments in several studies. For example, in the EMILIA trial, T-DM1 showed significant improvements in safety and effectiveness compared to a combination of other drugs, capecitabine and lapatinib. This suggests that T-DM1 is a strong option for patients who have already tried other treatments.
12345What safety data is available for the treatment of Atezolizumab + Trastuzumab Emtansine for breast cancer?
The safety profile of Trastuzumab Emtansine (T-DM1) has been extensively studied in various trials and analyses. The EMILIA trial highlighted differences in safety between T-DM1 and capecitabine plus lapatinib, focusing on adverse events like grade ≥ 3 and grade 2 events. T-DM1 has shown improved tolerability compared to standard treatments in phase I, II, and III studies. However, there are reports of serious adverse events, such as a case of fatal acute eosinophilic pneumonia. A pharmacovigilance study identified common adverse events for T-DM1, including decreased platelet count and hepatopulmonary syndrome, with a higher incidence of fatal outcomes in the hepatobiliary system. Advanced age and male gender are risk factors for fatal adverse events. Overall, T-DM1 is associated with hematological, hepatobiliary, and nervous system toxicities, among others.
14678Is the drug Trastuzumab Emtansine a promising treatment for breast cancer?
Yes, Trastuzumab Emtansine is a promising drug for breast cancer. It combines the cancer-fighting abilities of trastuzumab with a powerful agent called DM1, showing better results and being easier to tolerate than standard treatments for HER2-positive breast cancer.
135910Eligibility Criteria
This trial is for individuals with HER2-positive breast cancer who've had preoperative chemotherapy and surgery but still have invasive disease. They should be in good health, with a life expectancy of at least 6 months, and must not have stage IV cancer or a history of certain other cancers within the last 5 years.Inclusion Criteria
I've completed chemotherapy including treatments with taxane and trastuzumab.
It has been less than 12 weeks since my primary surgery.
You are expected to live for at least 6 more months.
+8 more
Exclusion Criteria
I have an active liver disease.
You have a history of autoimmune disease or weak immune system.
I have moderate to severe numbness, tingling, or pain in my hands or feet.
+8 more
Participant Groups
The study tests if Atezolizumab (an immunotherapy drug) or placebo, combined with Trastuzumab Emtansine (a targeted therapy), can prevent cancer recurrence in patients post-surgery. Participants are randomly assigned to one of two groups and treatment efficacy and safety are compared.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm B: Atezolizumab + Trastuzumab EmtansineExperimental Treatment3 Interventions
Participants will receive an IV infusion of atezolizumab prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles.
Group II: Arm A: Placebo + Trastuzumab EmtansineActive Control3 Interventions
Participants will receive an intravenous (IV) infusion of placebo prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles.
Trastuzumab is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Herceptin for:
- Early breast cancer
- Metastatic breast cancer
- Advanced gastric cancer
🇺🇸 Approved in United States as Herceptin for:
- Adjuvant treatment of HER2-positive breast cancer
- Metastatic breast cancer
- Advanced gastric cancer
🇨🇦 Approved in Canada as Herceptin for:
- Early breast cancer
- Metastatic breast cancer
- Advanced gastric cancer
🇯🇵 Approved in Japan as Herceptin for:
- Breast cancer
- Gastric cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Charleston Oncology, P .ACharleston, SC
Cooper Cancer InstituteCamden, NJ
Kaiser Permanente - VallejoVallejo, CA
Cooper Cancer InstituteVoorhees, NJ
More Trial Locations
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Who Is Running the Clinical Trial?
Hoffmann-La RocheLead Sponsor
References
Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: an integrated safety analysis. [2019]The antibody-drug conjugate trastuzumab emtansine (T-DM1) combines the cytotoxic activity of DM1 with the human epidermal growth factor receptor 2 (HER2) -targeted, antitumor properties of trastuzumab. T-DM1 has shown activity in phase I and II single-arm studies in patients with pretreated HER2-positive metastatic breast cancer (MBC) and has demonstrated superior efficacy and improved tolerability versus standard MBC treatments in randomized phase II and III studies. This analysis, combining available data from all single-agent T-DM1 studies to date, was conducted to better define the T-DM1 safety profile.
A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. [2022]To determine whether the antibody-drug conjugate trastuzumab emtansine (T-DM1), which combines human epidermal growth factor receptor 2 (HER2) -targeted delivery of the potent antimicrotubule agent DM1 with the antitumor activity of trastuzumab, is effective in patients with HER2-positive metastatic breast cancer (MBC) who have previously received all standard HER2-directed therapies.
Trastuzumab emtansine in breast cancer. [2019]Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC) composed of trastuzumab, a stable linker (MCC), and the cytotoxic agent DM1 (derivative of maytansine). Administration of T-DM1 leads to limited systemic exposure of free DM1, with no evidence of DM1 accumulation after repeated dosing.
Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System. [2019]Trastuzumab emtansine (T-DM1, KADCYLA(®)) is an antibody-drug conjugate comprised of the cytotoxic agent DM1 and trastuzumab (HERCEPTIN(®)). The safety profile of T-DM1 in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane was investigated in the phase III EMILIA trial. The trial demonstrated clinically and statistically meaningful differences in the safety profile between T-DM1 and capecitabine plus lapatinib (CAP + LAP). The objective of this study was to estimate the costs of managing treatment-related grade ≥ 3 adverse events (AEs) that occurred in ≥ 2% of patients and grade 2 AEs that occurred in ≥ 5% of patients taking T-DM1 compared with patients taking CAP + LAP based on the EMILIA trial, from the perspective of Canadian public payers.
Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B). [2021]Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer.
Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2-Positive Advanced Breast Cancer. [2022]Tolerability and safety of trastuzumab emtansine (T-DM1) was investigated in Japanese patients with HER2-positive advanced breast cancer who were previously treated with chemotherapy and trastuzumab.
Adverse Event Profile Differences between Trastuzumab Emtansine and Trastuzumab Deruxtecan: A Real-world, Pharmacovigilance Study. [2023]Introduction: Trastuzumab emtansine(T-DM1) and trastuzumab deruxtecan (T-DXd, formerly DS-8201a), the human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC), are commonly used in metastatic breast cancer. However, their real-world safety profile has not been adequately compared. Objective: We aimed to investigate the adverse event (AE) profile of T-DM1 and T-DXd reported by the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: All indications were searched for T-DM1 and T-DXd, as primary suspected drugs, from FAERS data (January 2004 to June 2023). Disproportionality analyses were performed by reporting odds ratios (ROR) and proportional reporting ratio (PRR). The odds ratio (OR) of fatal AEs associated with T-DM1 and T-DXd under different exposure factors were performed by univariate and multivariate logistical regression analysis. Results: 3723 and 2045 reports of T-DM1 and T-DXd were submitted to FAERS. Finally, 94 and 61 significant signals for T-DM1 and T-DXd were systematically analyzed. The valid AEs with the highest frequency and the strongest signal intensity for T-DM1 were platelet count decreased (n=108) and hepatopulmonary syndrome (ROR=680.42), respectively. Interstitial lung disease (n=262, ROR=82.55) and pneumonitis (n=89, ROR = 48.34) showed both high frequency and strong signal intensity for T-DXd. The proportion of AEs in each SOC system was different. T-DM1 had a greater proportion of valid AEs in the nervous system, musculoskeletal system, hepatobiliary system, ocular system, cardiac system and hematologic system(p<0.05). T-DXd had a greater proportion of valid AEs in the skin disorders, respiratory system, infestations, general system and gastrointestinal system(p<0.05). Furthermore, the analysis of fatal AEs in four systems revealed that T-DXd exhibited a significantly higher proportion of fatal outcomes in the hematologic and respiratory system compared to T-DM1. Conversely, T-DM1 had a significantly higher proportion of fatal outcomes in the hepatobiliary system. Neither T-DM1 nor T-DXd exhibited a high mortality ratio in the cardiac system. Logistic regression analysis indicated that advanced age (≥65 years) and male gender were identified as independent risk factors of fatal AEs for both T-DM1 and T-DXd. Additionally, the drug combination therapy, particularly with a CYP3A4 inhibitor, was found to be a risk factor for fatal AEs specifically related to T-DXd. Conclusions: Hematological and respiratory toxicity of T-DXd and hepatobiliary toxicity of T-DM1 exhibited a high incidence of fatal outcomes. It is crucial to identify high-risk factors and enhance the monitoring of AEs during clinical application.
Acute eosinophilic pneumonia: a fatal reaction to ado-trastuzumab. [2023]Ado-trastuzumab emtansine (T-DM1) is a monoclonal antibody drug conjugate approved for the treatment of HER2-positive breast cancers. Presented here is a case report of a patient who developed fatal pulmonary toxicity in the form of acute eosinophilic pneumonia while undergoing treatment with T-DM1. Prior to beginning T-DM1 therapy, this patient had been treated with two HER2-targeted agents (trastuzumab, pertuzumab) per National Comprehensive Cancer Network (NCCN) guidelines. This case represents a novel presentation of toxicity associated with T-DM1 while perhaps demonstrating additive toxicity associated with multiple lines of HER2 targeted therapies.
Lacrimal drainage system stenosis associated with Trastuzumab emtansine (Kadcyla®, T-DM1) administration: a case report. [2020]Trastuzumab emtansine (Kadcyla®, T-DM1) is an antibody-drug conjugate used to treat HER2 (human epidermal growth factor receptor 2) overexpressing metastatic breast cancer. In this report, we present the first case of lacrimal drainage system stenosis identified after T-DM1 administration, and its successful treatment with a topical steroid.
Trastuzumab emtansine for HER2-positive advanced breast cancer. [2022]Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent DM1. The antibody and the cytotoxic agent are conjugated by means of a stable linker.