Abstract LBO1-01: Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for early-stage triple-negative breast cancer: Updated event-free survival results from the phase 3 KEYNOTE-522 study

Abstract Background: In KEYNOTE-522 (NCT03036488), neoadjuvant pembrolizumab (pembro) plus chemotherapy (chemo) followed by adjuvant pembro showed statistically significant and clinically meaningful improvements in pathological complete response (pCR) and event-free survival (EFS) compared with neoadjuvant placebo (pbo) plus chemo followed by adjuvant pbo in patients (pts) with early-stage triple-negative breast cancer (TNBC). Here, we present updated EFS results after a median follow-up of ~5 y. Methods: Eligible pts with previously untreated, non-metastatic, centrally confirmed TNBC (stage T1c N1-2 or T2-4 N0-2 per American Joint Committee on Cancer) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or placebo (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. Dual primary endpoints are pCR (ypT0/Tis ypN0) and EFS (time from randomization to disease progression that precluded definitive surgery, local/distant recurrence, second primary cancer, or death from any cause). Results: 1174 pts were randomized to pembro (n=784) or pbo (n=390) group. At data cutoff (March 23, 2023), median follow-up was 63.1 mo. 145 pts (18.5%) in the pembro group and 108 pts (27.7%) in the pbo group had an EFS event (hazard ratio [HR] 0.63 [95% CI, 0.49-0.81]). The 60-mo EFS rate (95% CI) was 81.3% (78.4-83.9) vs 72.3% (67.5-76.5), respectively; the median was not reached in either group. The benefit of neoadjuvant pembro + chemo followed by adjuvant pembro versus neoadjuvant chemo alone was consistent with the primary EFS results in all 5 sensitivity analyses, showing durable and robust EFS benefit in the pembro arm. The EFS benefit with pembro was consistent across prespecified subgroups, including PD-L1 expression, nodal status, disease stage, menopausal status, HER2 status, and lactate dehydrogenase (LDH) level (table). In a prespecified, non-randomized, exploratory analysis, 5-yr EFS rates in the pembro and pbo groups were 92.2% vs 88.2% in pts with a pCR, and 62.6% vs 52.3% in pts without a pCR. Additional analyses will be included in the presentation. Follow-up for OS is ongoing Conclusions: Neoadjuvant pembro + chemo followed by adjuvant pembro continues to show a clinically meaningful improvement in EFS compared with neoadjuvant chemo alone in pts with early-stage TNBC. This is seen across subgroups and regardless of the pCR outcome. Table. EFS results in overall population and by subgroup Citation Format: Peter Schmid, Javier Cortés, Rebecca Dent, Lajos Pusztai, Heather McArthur, Sherko Küemmel, Carsten Denkert, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, Theodoros Foukakis, Marie-Ange Mouret-Reynier, Marta Ferreira, Seock-Ah Im, Fatima Cardoso, Yu Ding, Wilbur Pan, Konstantinos Tryfonidis, Joyce O'Shaughnessy. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for early-stage triple-negative breast cancer: Updated event-free survival results from the phase 3 KEYNOTE-522 study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr LBO1-01.