First-Line Pembrolizumab Combo Improves PFS in Patients With Extensive-Stage SCLC

First-line therapy with pembrolizumab plus etoposide and platinum (EP) led to significantly improved progression-free survival (PFS) compared with placebo plus EP in patients with extensive-stage small-cell lung cancer (ES-SCLC; J Clin Oncol. 2020 May 29. Epub ahead of print).

“Pembrolizumab monotherapy has shown antitumor activity in patients with [SCLC],” wrote Charles M. Rudin, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, and co-investigators, who sought to compare pembrolizumab plus etoposide and platinum (EP) with placebo plus EP in treatment-naïve patients with ES-SCLC.

A total of 453 patients with ES-SCLC were included in the double-blind, phase 3 KEYNOTE-604 clinical trial and randomized in a 1:1 ratio to receive pembrolizumab 200 mg once every 3 weeks plus 4 cycles of EP (n = 228) or saline placebo for up to 35 cycles plus 4 cycles of EP (n = 225).

The main end points of the study were PFS and overall survival (OS) in the intention-to-treat population, and secondary end points included the objective response rate (ORR) and duration of response.

Of note, the prespecified efficacy boundaries were one-sided P = .0048 and .0128 for PFS and OS, respectively.

Findings demonstrated a significant improvement in PFS with pembrolizumab plus EP versus placebo plus EP (hazard ratio [HR], 0.75; 95% CI, 0.61-0.91; P = .0023), and estimated 12-month PFS rates were 13.6% and 3.1%, respectively.

According to Dr Rudin et al, the significance threshold was not met despite pembrolizumab plus EP prolonging OS (HR, 0.80; 95% CI, 0.64-0.98; P = .0164).

The estimated 24-month OS rates were 22.5% and 11.2% with pembrolizumab plus EP and placebo plus EP, respectively. The ORR was 70.6% and 61.8%, respectively, and the estimated percentage of responders maintaining response at 12 months was 19.3% and 3.3%, respectively.

Any-cause adverse events in the pembrolizumab plus EP and placebo plus EP arms were grade 3-4 in 76.7% and 74.9% of patients, respectively; grade 5 in 6.3% and 5.4% of patients, respectively. These adverse events led to discontinuation of any drug in 14.8% and 6.3% of patients, respectively.

“Pembrolizumab plus EP significantly improved PFS compared with placebo plus EP as first-line therapy for patients with ES-SCLC,” Dr Rudin and colleagues concluded.

“No unexpected toxicities were seen with pembrolizumab plus EP. These data support the benefit of pembrolizumab in ES-SCLC,” they added.—Hina M. Porcelli