FP13.02 Pembrolizumab + Pemetrexed-Platinum vs Pemetrexed-Platinum for Metastatic NSCLC: 4-Year Follow-up From KEYNOTE-189

In the randomized, double-blind, phase 3 KEYNOTE-189 trial (NCT02578680) pembrolizumab plus pemetrexed-platinum chemotherapy significantly improved OS and PFS vs placebo in patients with previously untreated metastatic nonsquamous NSCLC without sensitizing EGFR/ALK alterations, regardless of PD-L1 expression. We present efficacy safety outcomes after ?4 years follow-up. Patients were randomized (2:1) to intravenous 200 mg or Q3W for up 35 cycles (2 years). All received pemetrexed investigator’s choice carboplatin/cisplatin 4 cycles, followed by maintenance pemetrexed. Treatment continued until radiographic progression/unacceptable toxicity. Crossover from monotherapy was permitted PD. who experienced SD better during initial treatment crossover phases then PD at any time follow-up period could receive second-course (17 cycles). The primary endpoints PFS. 616 (pembrolizumab pemetrexed-platinum, n=410; n=206). Median (range) randomization data cutoff (August 28, 2020) 46.3 (41.8–54.1) months. 84 (40.8%) control group crossed over on-study. Efficacy are summarized Table. (95% CI) 22.0 (19.5?24.5) months 10.6 (8.7?13.6) (hazard ratio [HR], 0.60; 95% CI, 0.50?0.72). 3-year rate 31.3% 17.4%. 9.0 (8.1?10.4) 4.9 (4.7?5.5) months, respectively (HR, 0.50; 0.41?0.59). Grade 3?5 AEs occurred 72.1% 67.3% group. Among 56 completed years) pembrolizumab, 49 (87.5%) had an objective response (CR, n=6; PR, n=43) 7 (12.5%) SD. 45 (80.4%) alive (28 PD), 2-year completion 79.6%. At cutoff, initiated pembrolizumab.Table 1Patients Characteristics Subgroups Defined TPSaITTN=616TPS ?50% n=202TPS 1%-49% n=186TPS <1% n=190OS HR CI)b0.60 (0.50–0.72)0.71 (0.50–1.00)0.66 (0.47–0.93)0.52 (0.37–0.72)3-yr rate,b %31.3 17.443.7 30.028.3 17.223.3 5.3PFS CI)b,c0.50 (0.41–0.59)0.36 (0.26–0.49)0.54 (0.39–0.76)0.68 (0.49–0.93)PFS2 CI)b,c,d0.52 (0.43–0.63)0.55 (0.39–0.77)0.59 (0.42–0.83)0.49 (0.35–0.68)ORR,c %48.3 19.962.1 25.750.0 20.733.1 14.3Median DOR,b,c mo12.6 7.115.1 7.113.6 7.610.8 7.8DOR, duration response; ITT, intention-to-treat; TPS, tumor proportion score. aAll pemetrexed-platinum. bKaplan-Meier estimate. cPer RECIST version 1.1 blinded independent central review. dPFS2 defined as second/subsequent progression on next-line treatment/death (per investigator assessment per 1.1). Open table a new tab DOR, With follow-up, provide benefit alone irrespective durable responses most cutoff. Toxicity manageable. Pembrolizumab remains standard-of-care therapy newly diagnosed NSCLC.