As reported in JAMA by Cheng et al, an interim analysis of the phase III ASTRUM-005 trial has shown that the addition of the PD-1 inhibitor serplulimab to chemotherapy improved overall survival in the first-line treatment of patients with extensive-stage small cell lung cancer (SCLC).
Study Details
The double-blind trial included 585 patients from sites in China, Georgia, Poland, Russia, Turkey, and Ukraine. They were randomly assigned 2:1 between September 2019 and April 2021 to receive serplulimab at 4.5 mg/kg (n = 389) or placebo (n = 196) every 3 weeks plus etoposide at 100 mg/m2 on days 1 to 3 and carboplatin area under the curve = 5 (up to 750 mg) on day 1 every 3 weeks for up to 12 weeks. The primary endpoint was overall survival; the prespecified significance threshold at the interim analysis was a two-sided P < .012. In total, 67% of patients in the serplulimab group and 71% in the control group were Asian.
Overall Survival
At data cutoff in October 2021 for the interim analysis, median follow-up was 12.3 months (range = 0.2–24.8 months). Median overall survival was 15.4 months (95% confidence interval [CI] = 13.3 months–not evaluable) in the serplulimab group vs 10.9 months (95% CI = 10.0–14.3 months) in the control group (hazard ratio [HR] = 0.63, 95% CI = 0.49–0.82, P < .001).
KEY POINTS
- The addition of the PD-1 inhibitor serplulimab to chemotherapy significantly improved overall survival at interim analysis.
- Median overall survival was 15.4 vs 10.9 months.
Median progression-free survival on independent radiology review committee assessment was 5.7 months (95% CI = 5.5–6.9 months) in the serplulimab group vs 4.3 months (95% CI = 4.2–4.5 months) in the placebo group (HR = 0.48, 95% CI = 0.38–0.59). Objective response was observed in 80.2% vs 70.4% of patients, with complete response seen in 0.8% vs 0%. Median response durations were 5.6 vs 3.2 months.
Adverse Events
Treatment-related grade ≥ 3 adverse events occurred in 33.2% of patients in the serplulimab group and in 27.6% of those in the control group; the most common in both groups were decreased neutrophils (14.1% vs 13.8%), decreased white blood cells (8.5% vs 8.7%), and decreased platelets (6.2% vs 8.2%). Treatment was discontinued due to treatment-related adverse events in 4.9% vs 4.1% of patients. Immune-related adverse events of any grade were reported in 37.0% vs 18.4% of patients (grade ≥ 3 in 9.5% vs 5.6%); those more common in the serplulimab group included hypothyroidism (11.6% vs 1.5%) and hyperthyroidism (9.0% vs 3.1%). Death due to adverse events attributed to serplulimab occurred in three patients (0.8%), with causes consisting of acute coronary syndrome, pyrexia, and decreased platelet count. Treatment-related death occurred in one patient in the control group (0.5%) due to thrombocytopenia.
The investigators concluded, “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.”
Ying Cheng, MD, of the Department of Oncology, Jilin Cancer Hospital, Changchun, China, is the corresponding author for the JAMA article.
Disclosure: This study was funded by Shanghai Henlius Biotech, Inc. For full disclosures of the study authors, visit jamanetwork.com.
