First-Line Serplulimab Plus Chemotherapy Improves Survival Outcomes in Extensive-Stage Small Cell Lung Cancer

The programmed death ligand-1 (PD-L1) inhibitor serplulimab plus chemotherapy prolonged progression free survival (PFS) and overall survival (OS) of patients with extensive-stage small-cell lung cancer (SCLC) who had not previously received systemic therapy, compared to placebo plus chemotherapy, according to interim analysis results from the ASTRUM-005 trial.

While combinations of atezolizumab or durvalumab plus chemotherapy have been approved for first-line treatment this patient population, Ying Cheng, MD, Department of Oncology, Jilin Cancer Hospital, Changchun, China, and colleagues explained, “improvements in overall survival with the approved PD-L1 inhibitors were modest, suggesting an unmet clinical need for more effective treatments in patients with extensive-stage SCLC.”

This international, double-blind, randomized phase 3 clinical trial enrolled 585 patients with extensive-stage SCLC who had not had any previous systemic therapy across 6 countries in Europe and Asia. Patients were randomized on a 2-to-1 basis to receive intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks and either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. The primary end point of the trial was OS. Secondary end points included PFS and safety.

At data cutoff of October 22, 2021, the median follow-up duration was 12.3 months. At this point, 42.1% of patients finished the trial, with 79.5% discontinuing study treatment (75.1% of the serplulimab arm; 88.3% of the placebo arm). The most common reason for study treatment discontinuation was disease progression. Patients who received ≥1 dose of study treatment were included in the primary analysis and safety population.

The median OS was 15.4 months (95% confidence interval [CI], 13.3 months to not evaluable) in the serplulimab arm and 10.9 months (95% CI, 10 to 14.3 months) with in the placebo arm. Median PFS was 5.7 months (95% CI, 5.5 to 6.9 months) and 4.3 months (95% CI, 4.2 to 4.5 months) in the serplulimab and placebo arms, respectively (hazard ratio [HR] 0.48 [95% CI, 0.38 to 0.59]).

There were 69.9% of patients in the serplulimumab arm and 56.1% in the placebo arm who experienced treatment-related adverse events. The most common were anemia, decreased white blood cell count, decreased neutrophil count, and decreased platelet count. Among patients treated with serpulimab, grade ≥3 treatment-related adverse events occurred in 32.2% (n = 129) of patients vs 27.6% (n = 54) in the placebo arm, the most common being decreased neutrophil count, decreased white blood cell count, decreased platelet count, and anemia. There were 4 deaths determined to be caused by treatment-related adverse events: 3 attributed to serplulimab (acute coronary syndrome, pyrexia, and a decreased platelet count) and 1 attributed to placebo (thrombocytopenia). All of these 4 treatment-related adverse events resulting in death were immune-related.

The study authors noted the lack of a head-to-head comparison of serplulimab to atezolizumab or durvalumab plus chemotherapy — this was due to those combinations not being approved in this patient population in China at the time of the start of the trial — as a limitation. Additionally, there were a small number of patients with brain metastases enrolled and carboplatin was the only platinum-based chemotherapy agent used in the trial.

 “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,” Dr Cheng and colleagues concluded.

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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