- In its first test in high-risk, early breast cancer (eBCa), pembrolizumab plus neoadjuvant chemotherapy (NACT) more than doubles the rate of pathologic complete response (pCR) than NACT alone in a phase 2 trial.
Why this matters
- Findings justify progression to a phase 3 trial.
- Open-label, multicenter, adaptively randomized phase 2 I-SPY2 trial comparing pembrolizumab (n=69; 200 mg intravenous [IV] every 3 weeks for 4 cycles) along with standard NACT (paclitaxel for 4 cycles followed by doxorubicin plus cyclophosphamide) vs standard NACT alone (n=181).
- High-risk patients were stages II-III invasive breast cancer with more than low-risk MammaPrint results.
- Primary outcome was pCR (absence of invasive tumor in breast and regional lymph nodes at surgery).
- Funding: Quantum Leap Healthcare Collaborative.
- The 3 pembrolizumab groups (vs NACT alone group) had a >2x higher rate of pCR and high predictive probability of success in phase 3 trial:
- HER2- breast cancer: 44% vs 17% pCR in controls, translating to 98.5% probability of success;
- HR+/HER2- breast cancer: 30% vs 13% in controls, translating to 99.6% probability of success; and
- Triple-negative breast cancer: 60% vs 22% in controls, translating to 83.4% probability of success.
- The pembrolizumab group had lower residual cancer burden.
- The pembrolizumab group had expected immune-related endocrinopathies.
- Open-label design.