Pembrolizumab (Pembro) Vs Paclitaxel (Ptx) For Previously Treated Advanced Gastric Or Gastroesophageal Junction (G/Gej) Cancer: Phase 3 Keynote-061 Trial.

4062 Background: Pembro has shown promising antitumor activity in patients (pts) with pretreated G/GEJ cancer. KEYNOTE-061 (NCT02370498) was a global phase 3 study of pembro vs PTX for previously treated advanced G/GEJ adenocarcinoma that progressed after first-line chemo containing platinum and fluoropyrimidine. Methods: Eligible pts were randomized to pembro 200 mg Q3W or standard-dose PTX. Randomization was stratified by geographic region, TTP on first-line therapy, and PD-L1 combined positive score (CPS). Primary end points were OS (efficacy boundary, one-sided P = .0135) and PFS in the CPS ≥1 population. Results: 395/592 pts enrolled had PD-L1 CPS ≥1: 196 assigned to pembro, 199 to PTX. After median follow-up of 8 mo, 7.8% of pts completed or remained on pembro vs 0% on PTX. Median OS was 9.1 mo with pembro vs 8.3 mo with PTX (HR 0.82, one-sided P = .042) (Table). 12-mo OS rates were 39.8% vs 27.1%; 18-mo rates were 25.7% vs 14.8%. There was no difference in PFS or ORR, but pembro responses were more durable (Table). Pembro treatment effect was more evident in pts with ECOG PS 0 (HR 0.69; 95% CI 0.49-0.97) or GEJ tumors (HR 0.61; 95% CI 0.41-0.90). In post-hoc analysis, the pembro treatment effect for OS was greater for CPS ≥5 (HR 0.73; 95% CI 0.52-1.03) and ≥10 (HR 0.64; 95% CI 0.41-1.02). In all pts, grade 3-5 drug-related AE incidence was 14.3% with pembro vs 34.8% with PTX; 3.1% vs 5.4% discontinued due to drug-related AEs. Conclusions: Pembro reduced the risk of death by 18% vs PTX in pts with previously treated G/GEJ cancer and PD-L1 CPS ≥1, although this difference was not statistically significant. Pembro had a better safety profile than PTX. Pembro treatment effect was more evident in pts with ECOG PS 0 and with increasing PD-L1 expression. Trials of pembro in G/GEJ cancer are ongoing. Clinical trial information: NCT02370498. Pembro N = 196 PTX N = 199 OS Median (95% CI), mo 9.1 (6.2-10.7) 8.3 (7.6-9.0) HR (95% CI) 0.82 (0.66-1.03) P .042 PFSa Median (95% CI), mo 1.5 (1.4-2.0) 4.1 (3.1-4.2) HR (95% CI) 1.27 (1.03-1.57) P .98 ORR,a % (95% CI) 15.8 (11.0-21.7) 13.6 (9.1-19.1) DOR,a median (range) 18.0 (1.4+ to 26.0+) 5.2 (1.3+ to 16.8) ≥12 mo, % 59.5 29.5 aAssessed per RECIST v1.1 by blinded, independent central review.