Atezolizumab (PD-L1) + trastuzumab/pertuzumab chemo misses EFS/DFS lift in high-risk early HER2+ breast cancer

In the Phase III IMpassion050 trial (NCT03726879), atezolizumab (anti–PD-L1) was added to neoadjuvant pertuzumab + trastuzumab + chemotherapy and continued after surgery with HER2-directed therapy. Among 454 patients with high-risk early HER2+ breast cancer and ~44 months of follow-up, 3-year EFS was 91.4% with atezolizumab vs 89.0% with placebo (HR 0.90, 95% CI 0.50–1.59), while 3-year DFS among patients receiving surgery and postneoadjuvant therapy was 92.9% vs 88.5% (HR 0.71, 95% CI 0.38–1.32)—neither a significant improvement. Adverse events of special interest were more frequent with atezolizumab (59.4% vs 47.0%). The treatment landscape has also moved since the trial began: in May 2026, T-DXd gained U.S. approvals both as neoadjuvant T-DXd followed by THP for stage II/III HER2+ disease and as adjuvant therapy for residual invasive disease after neoadjuvant HER2-directed/taxane treatment.