Serplulimab plus chemotherapy improves survival in Extensive-Stage Small Cell Lung Cancer: JAMA

Programmed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC.

A study was conducted to evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC.

This international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021.

Patients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks. The primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P < .012). There were 13 secondary outcomes, including progression-free survival and adverse events.

Results:

• Among the 585 patients who were randomized, 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment.
• All patients received study treatment and were included in the primary analyses.
• As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months).
• The median overall survival was significantly longer in the serplulimab group than in the placebo group
• The median progression-free survival also was longer in the serplulimab group than in the placebo group
• Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group.

Thus, among patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population.

Reference:

Cheng Y, Han L, Wu L, et al. Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial. JAMA. 2022;328(12):1223–1232. doi:10.1001/jama.2022.16464

Keywords:

Cheng Y, Han L, Wu L, Effect, First-Line, Serplulimab, Placebo, Added, Chemotherapy, Survival, Patients, Extensive-Stage, Small, Cell, Lung, Cancer