In a 4-year follow-up of the Chinese phase III GEMSTONE-302 trial reported in The Lancet Oncology, Zhou et al examined the survival benefit of adding the PD-L1 inhibitor sugemalimab to first-line platinum-based chemotherapy in patients with metastatic non–small cell lung cancer (NSCLC) with no known sensitizing EGFR, ALK, ROS1, or RET genomic alterations.
The primary analysis of the trial showed significant progression-free and overall survival benefits with the addition of sugemalimab.
Study Details
In the multicenter double-blind trial, 479 patients with squamous or nonsquamous disease were randomly assigned 2:1 between December 2018 and May 2020 to receive sugemalimab (n = 320) or placebo (n = 159) plus platinum-based chemotherapy.
Key Findings
At data cutoff (in May 2023), median follow-up was 43.5 months (interquartile range [IQR] = 41.2–46.9 months) in the sugemalimab group and 43.0 months (IQR = 40.7–44.8 months) in the control group.
Median progression-free survival was 9.0 months (95% confidence interval [CI] = 7.4–10.9 months) in the sugemalimab group vs 4.9 months (95% CI = 4.8–5.2 months) in the control group (hazard ratio [HR] = 0.49, 95% CI = 0.39–0.60).
A total of 29% of the control group crossed over to receive sugemalimab monotherapy and 20% received other subsequent immunotherapy.
Median overall survival was 25.2 months (95% CI = 20.1–30.2 months) in the sugemalimab group vs 16.9 months (95% CI = 12.8–20.7 months) in the control group (HR = 0.68, 95% CI = 0.54–0.85). The 4-year overall survival rates were 32.1% vs 17.3%. At 4 years, overall survival was 27.6% vs 11.7% among patients with squamous NSCLC and 35.5% vs 20.2% among those with nonsquamous NSCLC.
Overall, treatment-related grade 3 or 4 adverse events occurred in 56% of the sugemalimab group vs 57% of the control group; the most common were decreased neutrophils (33% vs 33%), decreased white blood cells (15% vs 17%), anemia (14% vs 11%), and decreased platelets (11% vs 9%). Treatment-related serious adverse events occurred in 26% vs 20% of patients. No additional treatment-related deaths were observed since the previous overall survival interim analysis, which showed treatment-related death in 3% vs 1% of patients. No new safety signals were identified.
The investigators concluded: "Sugemalimab with chemotherapy showed a superior long-term overall survival benefit compared with placebo with chemotherapy, as a first-line treatment for patients with NSCLC with no known sensitizing EGFR, ALK, ROS1, or RET genomic alterations. These results underscore the efficacy of sugemalimab plus platinum-based chemotherapy as a standard first-line treatment option for both squamous and nonsquamous metastatic NSCLC while maintaining a manageable safety profile."
Caicun Zhou, MD, PhD, of the Department of Oncology, Shanghai Pulmonary Hospital and Shanghai East Hospital, Tongji University School of Medicine, Shanghai, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by CStone Pharmaceuticals. For full disclosures of all study authors, visit thelancet.com.
