Efficacy of pembrolizumab (pembro) monotherapy versus chemotherapy for PD-L1–positive (CPS ≥10) advanced G/GEJ cancer in the phase II KEYNOTE-059 (cohort 1) and phase III KEYNOTE-061 and KEYNOTE-062 studies.
Zev A. Wainberg, Charles S. Fuchs, Josep Tabernero, Kohei Shitara, Kei Muro, Eric Van Cutsem, Yung‐Jue Bang, Hyun Cheol Chung, Kensei Yamaguchi, Eniko Varga, Jen‐Shi Chen, Daniel Hochhauser, Peter Thuss‐Patience, Salah‐Eddin Al‐Batran, Marcelo Garrido, Uma Kher, Chie‐Schin Shih, Sukrut Shah, Pooja Bhagia, Joseph Chao
Abstract
427 Background: Pts with advanced gastric/gastroesophageal junction (G/GEJ) cancer received pembro monotherapy (200 mg Q3W) 3L+ in cohort 1 of KEYNOTE-059 (NCT02335411), 2L in KEYNOTE-061 (NCT02370498), or 1L in KEYNOTE-062 (NCT02494583). We present efficacy data for patients with PD-L1 combined positive score (CPS) ≥10 tumors in these trials. Methods: In study 059, 46 pts in cohort 1 with PD-L1 CPS ≥10 received pembro. In study 061, 108 pts with PD-L1 CPS ≥10 received pembro (n=53) or chemotherapy (chemo; n=55). In study 062, 182 pts with CPS ≥10 received pembro (n=92) or placebo + chemo (n=90). Efficacy end points included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Results: Median follow-up in study 059 was 5.6 mo. Median OS with pembro was 7.9 mo (95% CI, 5.8-11.1), and 12-mo OS was 32.6%. PFS at 6 mo was 17.4%, ORR was 17.4%, and median DOR was 20.9 mo (2.8+ to 34.9+). In study 061, after a median follow-up of 8.8 mo, pembro prolonged OS vs chemo (median 10.4 vs 8.0 mo; HR, 0.64; 95% CI, 0.41-1.02); 12-mo OS was 45.3% for pembro and 23.6% for chemo. Median PFS was 2.7 mo for pembro and 3.4 mo for chemo (HR, 0.86; 95% CI, 0.56-1.33). ORR was 24.5% vs 9.1%, and median DOR was NR (4.1-26.0+) and 6.9 mo (2.6-6.9) for pembro vs chemo. In study 062, median follow-up was 17.4 mo for pembro and 10.8 mo for chemo. Pembro prolonged OS vs chemo (median 17.4 vs 10.8 mo; HR, 0.69; 95% CI, 0.49-0.97); 12-mo OS was 56.5% vs 46.7%. Median PFS was 2.9 mo vs 6.1 mo (HR, 1.09, 95% CI, 0.79-1.49). ORR was 25.0% vs 37.8%, and median DOR was 19.3 mo (1.4+ to 33.6+) vs 6.8 mo (1.5+ to 30.4+) for pembro vs chemo, respectively. Conclusions: Collectively, these data indicate that 1L, 2L, and 3L+ pembro monotherapy showed clinically meaningful efficacy in CPS ≥10, with a more durable response than chemotherapy. Clinical trial information: NCT02335411, NCT02370498, and NCT02494583. [Table: see text]