FP13.04 KEYNOTE-042 3-Year Survival Update: 1L Pembrolizumab vs Platinum-Based Chemotherapy for PD-L1+ Locally Advanced/Metastatic NSCLC

Abstract

In the KEYNOTE-042 study (NCT02220894), pembrolizumab significantly improved OS vs platinum-based chemotherapy as first-line treatment for locally advanced/metastatic NSCLC without sensitizing EGFR/ALK alterations with PD-L1 tumor proportion score (TPS) ≥1%. We present updated data from KEYNOTE-042 with >3 years follow-up from randomization, including an exploratory analysis of time to progression on next-line therapy (PFS-2). Outcomes in patients who completed 35 cycles of pembrolizumab and in those who received second-course treatment are also reported. Patients were randomized 1:1 to pembrolizumab 200 mg Q3W for 35 cycles or chemotherapy (carboplatin area under the curve 6/5 plus paclitaxel 200 mg/m2 or pemetrexed 500 mg/m2) Q3W for 4‒6 cycles with optional pemetrexed maintenance (nonsquamous only). Randomization was stratified by region (East Asia vs non–East Asia), histology (squamous vs nonsquamous), ECOG PS (0 vs 1), and PD-L1 TPS (≥50% vs 1%–49%). The primary endpoint was OS in prespecified TPS groups (≥50%, ≥20%, and ≥1%). Secondary endpoints included PFS, ORR, and safety. Patients randomized to pembrolizumab who completed 35 treatment cycles with SD or better or stopped treatment after confirmed CR could receive second-course pembrolizumab after PD if eligibility criteria were met. No alpha was assigned to these analyses. 1274 patients were randomized (pembrolizumab, n=637; chemotherapy, n=637). As of February 21, 2020, median (range) time from randomization to database cutoff was 46.9 (35.8‒62.1) months. Efficacy results are summarized in the Table. Treatment-related grade 3‒5 AEs occurred in 120 (18.9%) vs 256 patients (41.6%) in the pembrolizumab vs chemotherapy groups. 102 patients completed 35 cycles (∼2 years) of pembrolizumab. 86/102 (84.3%) had CR (n=2) or PR (n=84) as best response. 80/102 (78.4%) patients were alive at time of analysis. 1-year OS after completion of 35 cycles was 91.1% in patients with PD-L1 TPS ≥1%. Among 26 patients who received second-course pembrolizumab; ORR after initiation of second-course treatment was 15.4% (all PR), and the disease-control rate (CR+PR+SD) was 76.9%. 21/26 (80.8%) patients were alive at data cutoff.TableEfficacyPD-L1 TPS ≥50%PD-L1 TPS ≥20%PD-L1 TPS ≥1%Pembro (N=299)Chemo (N=300)Pembro (N=413)Chemo (N=405)Pembro (N=637)Chemo (N=637)Median OS,a,b mo (95% CI)20.0 (15.9‒24.2)12.2 (10.4‒14.6)18.0 (15.5‒21.5)13.0 (11.6‒15.3)16.4 (14.0‒19.6)12.1 (11.3‒13.3)HR (95% CI)0.68 (0.57‒0.82)0.75 (0.64‒0.88)0.80 (0.71‒0.90)3-y OS rate,a % (95% CI)31.3 (26.1‒36.6)18.4 (14.2‒23.0)28.3 (24.1‒32.8)18.8 (15.1‒22.8)25.3 (22.0‒28.7)16.7 (13.8‒19.7)Median PFS,a,b, c mo (95% CI)6.5 (5.9‒8.6)6.5 (6.2‒7.6)6.2 (5.1‒7.4)6.8 (6.3‒8.1)5.5 (4.3‒6.2)6.8 (6.4‒7.7)HR (95% CI)0.85 (0.72‒1.02)0.95 (0.82‒1.10)1.05 (0.93‒1.18)3-y PFS rate,a % (95% CI)14.5 (10.5‒19.0)5.3 (3.0‒8.7)13.2 (10.0‒16.9)4.7 (2.7‒7.5)11.0 (8.6‒13.7)4.1 (2.6‒6.2)Median PFS-2,a,d mo (95% CI)15.0 (11.6‒19.2)10.1 (8.9‒11.2)12.9 (10.9‒15.5)10.2 (9.0‒11.3)11.3 (10.1‒12.9)9.3 (8.6‒10.2)HR (95% CI)0.62 (0.52‒0.74)0.66 (0.57‒0.77)0.73 (0.65‒0.82)ORR,b %39.1 (33.6‒44.9)32.3 (27.1‒37.9)33.2 (28.6‒37.9)29.1 (24.8‒33.8)27.3 (23.9‒31.0)26.7 (23.3‒30.3)Median DOR,a mo (95% CI)27.3 (2.1+ to 56.0+)10.8 (1.8+ to 49.6+)22.3 (2.1+ to 56.0+)10.8 (1.8+ to 49.6+)22.3 (2.1+ to 56.0+)8.4 (1.8+ to 49.6+)Chemo, chemotherapy; Pembro, pembrolizumab. “+” indicates no progressive disease at the time of last disease assessment. aKaplan-Meier estimate. bOS and PFS were calculated from the time of randomization. cPer RECIST v1.1 by blinded independent central review. dPFS-2 was defined as time from randomization to subsequent disease progression after initiation of new anticancer therapy, or death from any cause, whichever occurred first. Open table in a new tab Chemo, chemotherapy; Pembro, pembrolizumab. “+” indicates no progressive disease at the time of last disease assessment. aKaplan-Meier estimate. bOS and PFS were calculated from the time of randomization. cPer RECIST v1.1 by blinded independent central review. dPFS-2 was defined as time from randomization to subsequent disease progression after initiation of new anticancer therapy, or death from any cause, whichever occurred first. With long-term follow-up, first-line pembrolizumab monotherapy continued to show improved OS, ORR and PFS-2 outcomes compared with platinum-based chemotherapy in patients with locally advanced/metastatic PD-L1–positive NSCLC without sensitizing EGFR/ALK alterations, with a manageable safety profile. Patients who completed 35 cycles of pembrolizumab had durable responses, and second-course pembrolizumab was feasible and associated with antitumor activity. These findings continue to support first-line pembrolizumab in patients with locally advanced/metastatic PD-L1–positive NSCLC without sensitizing EGFR/ALK alterations.