VP7-2021: KEYNOTE-522: Phase III study of neoadjuvant pembrolizumab + chemotherapy vs. placebo + chemotherapy, followed by adjuvant pembrolizumab vs. placebo for early-stage TNBC

KEYNOTE-522 (NCT03036488) is a phase III study of neoadjuvant pembrolizumab (pembro) + chemotherapy (chemo) vs. placebo (pbo) + chemo followed by adjuvant pembro vs. pbo in patients (pts) with early-stage TNBC. In prior interim analyses, pembro + chemo showed a significant improvement in pCR and a favorable trend in EFS. We present results from a prespecified interim analysis of KEYNOTE-522. Pts with previously untreated, non-metastatic, centrally confirmed TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or pbo, both given with 4 cycles of paclitaxel + carboplatin, then with 4 cycles of doxorubicin or epirubicin + cyclophosphamide. After definitive surgery, pts received adjuvant pembro or pbo for 9 cycles or until recurrence or unacceptable toxicity. Pts were stratified by nodal status (+ vs. −), tumor size (T1/T2 vs. T3/T4), and carboplatin schedule (Q3W vs. QW). Dual primary endpoints are pCR (ypT0/Tis ypN0) and EFS. 1174 pts were randomized to pembro (n=784) or pbo (n=390). At the March 23, 2021 data cutoff (median follow-up, 37.8 mo [range, 2.7-48.0]), 123 pts (15.7%) in the pembro group and 93 pts (23.8%) in the pbo group had an EFS event, defined as disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (HR 0.63 [95% CI, 0.48-0.82]; P=0.0003). The 36-mo EFS rate was 84.5% (95% CI, 81.7-86.9) in the pembro group vs. 76.8% (95% CI, 72.2-80.7) in the pbo group; median was not reached in either group. The most common EFS event was distant recurrence, in 60 pts (7.7%) in the pembro group vs. 51 pts (13.1%) in the pbo group. Pembro showed a favorable trend in OS (HR 0.72 [95% CI, 0.51-1.02]); follow-up is ongoing. Grade ≥3 treatment-related AE rates were 77.1% in the pembro group and 73.3% in the pbo group (death incidence, 0.5% vs. 0.3%, respectively); immune-mediated AEs of any grade occurred in 43.6% vs. 21.9%, respectively. Neoadjuvant pembro + chemo followed by adjuvant pembro showed a statistically significant and clinically meaningful improvement in EFS compared with neoadjuvant chemotherapy alone in pts with early-stage TNBC.