5-year update from KEYNOTE-407: Pembrolizumab plus chemotherapy in squamous non-small cell lung cancer (NSCLC)

Pembrolizumab (pembro) + platinum-based chemotherapy (chemo) significantly prolonged OS and PFS compared with placebo + chemo in patients (pts) with previously untreated, metastatic squamous NSCLC in the phase III KEYNOTE-407 study (NCT02775435). We report the 5-y outcomes in the ITT population and in pts who completed 35 cycles of pembro (∼2 y). Eligible pts were randomized 1:1 to receive pembro 200 mg or placebo + carboplatin and paclitaxel/nab-paclitaxel Q3W for 4 cycles, followed by pembro or placebo up to 35 cycles. Eligible pts in the placebo + chemo group were allowed to crossover on-study to up to 35 cycles of open-label pembro monotherapy upon unblinding after verification of PD by BICR. Primary endpoints were OS and PFS per RECIST v1.1 by BICR. Pts were randomized to pembro + chemo (n = 278) or placebo + chemo (n = 281). As of Feb 23, 2022, median time from randomization to data cutoff was 56.9 (range, 49.9–66.2) mo; 117 pts crossed over from the placebo + chemo group to receive pembro monotherapy, and an additional 26 pts received subsequent anti–PD-(L)1 therapy; the effective crossover rate was 51.1%. Median OS in the ITT population was 17.2 mo for the pembro + chemo group and 11.6 mo for the placebo + chemo group; HR, 0.71 (95% CI, 0.59–0.85). Respective 5-y OS rates were 18.4% and 9.7%. Additional efficacy outcomes are described in the table. Grade 3‒5 AEs occurred in 74.8% and 70.0% of pts in the pembro + chemo and placebo + chemo groups, respectively. Among 55 pts who completed 35 cycles of pembro, ORR was 90.9%, and 3-y OS rate after completion of 35 cycles (⁓5 y after randomization) was 69.5%.Table: 974MOITT populationPembrolizumab + chemotherapy n = 278Placebo + chemotherapy n = 281Median OS (95% CI), mo17.2 (14.4‒19.7)11.6 (10.1‒13.7)OS HR (95% CI)0.71 (0.59‒0.85)5-year OS rate, %18.49.7Median PFS (95% CI), mo8.0 (6.3‒8.5)5.1 (4.3‒6.0)PFS HR (95% CI)0.62 (0.52‒0.74)5-year PFS rate, %10.83.5ORR (95% CI), %62.2 (56.2‒68.0)38.8 (33.1‒44.8)Median DOR (range), mo9.0 (1.3+ to 61.5+)4.9 (1.3+ to 58.6+)–DOR ≥4 y; %21.616.0+ indicates no PD by time of last assessment. Open table in a new tab + indicates no PD by time of last assessment. After 5 y of follow-up, pembro + chemo continued to demonstrate prolonged OS and PFS vs chemo alone without increased toxicity. Most pts who completed 35 cycles had objective responses and were alive at data cutoff. These long-term data support use of pembro + chemo as a standard first-line treatment option for metastatic squamous NSCLC.