973MO KEYNOTE-189 5-year update: First-line pembrolizumab (pembro) + pemetrexed (pem) and platinum vs placebo (pbo) + pem and platinum for metastatic nonsquamous NSCLC

Abstract

Pembro + pem-platinum significantly improved survival vs pbo + pem-platinum in patients (pts) with previously untreated, metastatic nonsquamous NSCLC without sensitizing EGFR/ALK alterations, regardless of PD-L1 TPS, in the phase III KEYNOTE-189 study (NCT02578680). We report updated results with ∼5 y of follow-up. Pts were randomized 2:1 to receive pembro 200 mg or pbo Q3W for up to 35 cycles (2y). All pts also received pem and investigator’s choice of carboplatin/cisplatin for 4 cycles, followed by maintenance pem until PD/unacceptable toxicity. Crossover from the pbo + pem-platinum group to pembro monotherapy was permitted after PD. Primary endpoints were OS and PFS. Among 616 pts randomized (pembro + pem-platinum, n = 410; pbo + pem-platinum, n = 206), median time from randomization to data cutoff (Mar 8, 2022) was 64.6 (range, 60.1–72.4) mo. 116/202 (57.4%) treated pts crossed over from pbo + pem-platinum to anti–PD-(L)1 therapy during/outside the study. Median (95% CI) OS was 22.0 (19.5‒24.5) mo vs 10.6 (8.7‒13.6) mo with pembro + pem-platinum vs pbo + pem-platinum (HR, 0.60; 95% CI, 0.50‒0.72) and 5-y OS rates were 19.4% vs 11.3%, respectively. Median (95% CI) PFS was 9.0 (8.1‒10.4) mo vs 4.9 (4.7‒5.5) mo (HR, 0.50; 95% CI, 0.42‒0.60). Additional efficacy results are in the table. Among pts with ≥1 dose of assigned treatment, grade 3‒5 AEs occurred in 295/405 (72.8%) vs 136/202 (67.3%) of pts. Among 57 pts who completed 35 cycles of pembro, ORR was 86.0% (CR, n = 8; PR, n = 41); 3-y OS rate after completion of 35 cycles of pembro was 71.9%. First-line pembro + pem-platinum continued to show OS and PFS benefits with manageable toxicity vs pbo + pem-platinum, irrespective of PD-L1 expression. Pts who completed 35 cycles of pembro experienced durable responses. These data further support pembro + pem-platinum as a standard of care for metastatic nonsquamous NSCLC without sensitizing EGFR/ALK alterations.Table: 973MOITTN = 616TPS ≥50% n = 202TPS 1%‒49% n = 186TPS <1% n = 190OS HR (95% CI)a0.60 (0.50–0.72)0.68 (0.49–0.96)0.65 (0.46–0.90)0.55 (0.39–0.76)5-y OS ratea,%19.4 vs 11.329.6 vs 21.419.8 vs 7.79.6 vs 5.3PFS HR (95%CI)a,b0.50 (0.42–0.60)0.35 (0.25–0.49)0.57 (0.41–0.80)0.67 (0.49–0.92)ORRb, %48.3 vs 19.962.1 vs 25.750.0 vs 20.733.1 vs 14.3Median DORa,b mo (range)12.7 (1.1+ to 68.3+) vs 7.1 (2.4 to 31.5)15.3 (1.2+ to 68.3+) vs 7.1 (3.4 to 31.5)13.6 (2.1+ to 67.6+) vs 7.6 (2.4 to 31.0+)10.8 (1.1+ to 59.4+) vs 7.8 (4.1 to 28.3+)+, no PD at last follow up; DOR, duration of response. Data are for pembro + pem-platinum vs pbo + pem-platinum. aK-M estimate. bPer RECIST v1.1 by blinded independent central review. Open table in a new tab