Atezolizumab plus pertuzumab, trastuzumab, and chemotherapy in HER2-positive early breast cancer: final results of the phase III IMpassion050 trial.

BACKGROUND: The IMpassion050 (NCT03726879) primary analysis showed similar pathologic complete response (pCR) rates with/without the addition of neoadjuvant atezolizumab to pertuzumab, trastuzumab, and chemotherapy in high-risk human epidermal growth factor receptor 2-positive early breast cancer in the intention-to-treat and programmed death-ligand 1 (PD-L1)-positive populations. Safety was consistent with other atezolizumab combination studies. We report final analysis results. PATIENTS AND METHODS: Patients were randomized 1 : 1 to atezolizumab/placebo, plus pertuzumab, trastuzumab, and chemotherapy. Postsurgery, patients continued atezolizumab/placebo, plus pertuzumab and trastuzumab up to 1 year. Patients with residual disease could switch to trastuzumab emtansine plus atezolizumab/placebo for 14 cycles. Secondary endpoints included disease-free survival (DFS), event-free survival (EFS), and safety. Stratification factors were stage at diagnosis, hormone receptor (HR) status, and PD-L1 status. RESULTS: At data cut-off (24 August 2023), 411/454 patients remained on-study (atezolizumab arm, 206/226; placebo arm, 205/228). Median follow-up was 44.2 and 43.4 months, respectively. Three-year EFS rates were 91.4% (atezolizumab) versus 89.0% {placebo [stratified hazard ratio 0.90, 95% confidence interval (CI) 0.50-1.59]}. Among patients who had surgery and postneoadjuvant therapy (n = 434), 3-year DFS rates were 92.9% (atezolizumab) versus 88.5% [placebo (hazard ratio 0.71, 95% CI 0.38-1.32)]. Numerically higher 3-year EFS and DFS rates with atezolizumab were seen in patients with PD-L1-negative status, HR-positive status, and stage T2 disease. Numerical DFS improvements with atezolizumab occurred regardless of pCR. Adverse events (AEs) of special interest in the adjuvant setting were more frequent with atezolizumab (59.4% versus 47.0%; none grade 5). The most common AEs (≥10% of patients in either arm) were radiation skin injury (24.0% versus 19.4%), arthralgia (20.7% versus 17.1%), and diarrhea (20.7% versus 13.4%). CONCLUSIONS: There were no significant improvements in 3-year EFS (stratified hazard ratio: 0.90; 95% CI: 0.50-1.59) or DFS (unstratified hazard ratio: 0.71; 95% CI: 0.38-1.32) rates with the addition of atezolizumab. Safety remained consistent with the known profiles of the study drugs.