IMpassion050 Final Results: Atezolizumab Fails to Improve Long-Term Outcomes in High-Risk HER2-Positive Breast Cancer
核心洞察
Final IMpassion050 analysis found adding atezolizumab to pertuzumab, trastuzumab and chemotherapy did not significantly improve event-free or disease-free survival in high-risk HER2-positive early breast cancer (搜索).
Three-year event-free survival was 91.4% with atezolizumab versus 89.0% with placebo (stratified HR 0.90, 95% CI 0.50-1.59) after roughly 44 months of median follow-up.
Grade 3-4 adverse events during the adjuvant phase occurred in 28.6% of atezolizumab patients versus 19.4% with placebo, and the trial's monitoring committee stopped treatment early on benefit-risk grounds.
The final analysis of the phase III IMpassion050 trial, published in ESMO Open, shows that adding atezolizumab to pertuzumab, trastuzumab and chemotherapy did not significantly improve long-term outcomes in patients with high-risk HER2-positive early breast cancer (搜索). At a median follow-up of approximately 44 months, three-year event-free survival was 91.4% with atezolizumab versus 89.0% with placebo (stratified HR 0.90, 95% CI 0.50-1.59). Among the 434 patients who had surgery and received post-neoadjuvant therapy, three-year disease-free survival was 92.9% versus 88.5% (unstratified HR 0.71, 95% CI 0.38-1.32). Only 24 deaths had occurred among 454 randomized patients, so overall survival remains too immature for interpretation.
The results follow the previously reported primary endpoint failure. Pathologic complete response rates were 62.4% with atezolizumab versus 62.7% with placebo in the intention-to-treat population, and 64.2% versus 72.5% in PD-L1 (搜索)-positive tumors. Biomarker analyses of HER2 (搜索) IHC pattern, HER2 amplification, hormone receptor status and PIK3CA alterations did not identify a subgroup with a convincing differential pCR benefit. Numerical subgroup signals, including apparently greater effects in PD-L1-negative and hormone receptor-positive disease, involved few events and are described as hypothesis-generating only.
Safety data showed increased toxicity with atezolizumab. During the adjuvant phase, grade 3-4 adverse events occurred in 28.6% versus 19.4% of patients, serious adverse events in 13.4% versus 8.8%, and adverse events of special interest in 59.4% versus 47.0% for any grade. Immune-mediated hepatitis occurred in 22.1% versus 17.1% and immune-mediated pneumonitis in 4.1% versus 1.4%. Five deaths from adverse events occurred in the atezolizumab arm, two of which, septic shock and alveolitis, were considered related to treatment. The Independent Data Monitoring Committee recommended stopping study treatment in January 2021 on benefit-risk grounds.
The authors note that the phase III APTneo and ASTEFANIA trials, which are powered around event-free and invasive disease-free survival respectively, may clarify whether checkpoint blockade benefits a selected population with residual risk. They also highlight DESTINY-Breast11, in which trastuzumab deruxtecan-based regimens increased pCR rates in high-risk disease, as evidence that the HER2 (搜索)-positive treatment landscape is shifting toward more potent HER2-directed therapy.
Source: OncoDaily