Pembrolizumab Plus Chemotherapy in Squamous Non-Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report 5-year efficacy and safety outcomes from the phase III KEYNOTE-407 study (ClinicalTrials.gov identifier: NCT02775435). Eligible patients with previously untreated, metastatic squamous non-small-cell lung cancer (NSCLC) were randomly assigned 1:1 to pembrolizumab 200 mg or placebo plus carboplatin and paclitaxel/nab-paclitaxel once every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to 35 cycles. Primary end points were overall survival (OS) and progression-free survival (PFS) per RECIST version 1.1 by blinded independent central review (BICR). Five hundred fifty-nine patients were randomly assigned in the intention-to-treat population (pembrolizumab plus chemotherapy, n = 278; placebo plus chemotherapy, n = 281). The median time from random assignment to data cutoff was 56.9 (range, 49.9-66.2) months. OS and PFS were improved with pembrolizumab plus chemotherapy versus placebo plus chemotherapy (hazard ratio [95% CI], 0.71 [0.59 to 0.85] and 0.62 [0.52 to 0.74]), with 5-year OS rates of 18.4% versus 9.7%, respectively. Toxicity was manageable. Among 55 patients who completed 35 cycles of pembrolizumab, the objective response rate was 90.9% and the 3-year OS rate after completion of 35 cycles (approximately 5 years after random assignment) was 69.5%. Pembrolizumab plus chemotherapy maintained an OS and PFS benefit versus placebo plus chemotherapy in previously untreated, metastatic squamous NSCLC and is a standard-of-care first-line treatment option for metastatic squamous NSCLC regardless of programmed death ligand 1 expression.

FIG 1.

Kaplan-Meier estimates of OS and PFS in the (A and E) ITT population, (B and F) patients with PD-L1 TPS ≥ 50%, (C and G) patients with PD-L1 TPS 1%-49%, and (D and H) patients with PD-L1 TPS < 1%. chemo, chemotherapy; HR, hazard ratio; ITT, intention to treat; NR, not reached; OS, overall survival; PD-L1, programmed death ligand 1; PFS, progression-free survival; TPS, tumor proportion score.

FIG 2.

Patient response to pembrolizumab plus chemotherapy and placebo plus chemotherapy. (A) DOR in the ITT population and (B) time to response and DOR in patients who completed 35 cycles of pembrolizumab. Median PFS was NR (95% CI, 21.2 months to NR) among patients who completed 35 cycles. The PFS rate 3 years after completion of 35 cycles was 58.4% (95% CI, 39.8 to 73.0). chemo, chemotherapy; CR, complete response; DOR, duration of response; ITT, intention to treat; NR, not reached; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.

FIG A1.

Kaplan-Meier estimates of (A) OS and (B) PFS in patients with PD-L1 TPS ≥ 1%. chemo, chemotherapy; HR, hazard ratio; NR, not reached; OS, overall survival; PD-L1, programmed death ligand 1; PFS, progression-free survival; TPS, tumor proportion score.