Background
Multicentre, multinational, double-blind phase 3 trial in 1550 patients with stage II–III triple-negative breast cancer (TNBC). Tested adding the anti–PD-L1 antibody atezolizumab to sequential taxane–carboplatin–anthracycline neoadjuvant chemotherapy, followed by adjuvant atezolizumab.
Results
Interventions and follow up: Arm A: Atezolizumab + neoadjuvant paclitaxel/carboplatin → doxorubicin/cyclophosphamide, then adjuvant atezolizumab (n=773)
Arm B: Placebo + identical chemotherapy backbone (n=777)
Primary endpoint: Event-free survival (EFS)
mFollow up: 4-year EFS/OS rates reported
Results: EFS: HR 0.80 (95% CI 0.62–1.03); stratified log-rank P=.083; 4-yr EFS difference 3.3% — primary endpoint NOT met
OS: HR 0.86 (95% CI 0.62–1.19); 4-yr benefit 0.7%
Subgroup (exploratory): EFS benefit in clinically node-positive disease (Pinteraction=.039); basal-like immune-activated mRNA subset may benefit
Arm B: Placebo + identical chemotherapy backbone (n=777)
Primary endpoint: Event-free survival (EFS)
mFollow up: 4-year EFS/OS rates reported
Results: EFS: HR 0.80 (95% CI 0.62–1.03); stratified log-rank P=.083; 4-yr EFS difference 3.3% — primary endpoint NOT met
OS: HR 0.86 (95% CI 0.62–1.19); 4-yr benefit 0.7%
Subgroup (exploratory): EFS benefit in clinically node-positive disease (Pinteraction=.039); basal-like immune-activated mRNA subset may benefit
Adverse events
Grade ≥3 TEAE: 75.3% vs 73.4%
Immune-mediated: irAEs 27.6% vs 11.4%
Discontinuation (neoadjuvant): atezolizumab 25.5% vs placebo 18.8%
Immune-mediated: irAEs 27.6% vs 11.4%
Discontinuation (neoadjuvant): atezolizumab 25.5% vs placebo 18.8%
Conclusions
Adding atezolizumab to an anthracycline/taxane/carboplatin neoadjuvant regimen did not significantly improve EFS in stage II–III TNBC. This contrasts with the positive KEYNOTE-522 pembrolizumab result. Hypothesis-generating benefit in node-positive and basal-like immune-activated subsets requires prospective validation.
Key Limitations
Primary EFS did not reach significance (P=.083); node-positive and biomarker subset benefits are exploratory/post-hoc; chemotherapy backbone and checkpoint agent differ from KEYNOTE-522, limiting cross-trial inference; OS remains immature.
Clinical Context
Neoadjuvant–adjuvant pembrolizumab (KEYNOTE-522) is FDA-approved and preferred by NCCN, ASCO, and ESMO for stage II–III TNBC. Atezolizumab is not approved in early TNBC; this negative phase 3 does not support its use in this setting and reinforces pembrolizumab as the checkpoint inhibitor of choice.