In an interim analysis of the Chinese phase III GEMSTONE-301 study reported in The Lancet Oncology, Zhou et al found that the PD-L1 inhibitor sugemalimab prolonged progression-free survival vs placebo in patients with locally advanced unresectable stage III non–small cell lung cancer (NSCLC) without disease progression after definitive concurrent or sequential chemoradiation.
Study Details
In the multicenter double-blind trial, 381 patients enrolled irrespective of PD-L1 expression status were randomly assigned 2:1 between August 2018 and December 2020 to receive sugemalimab at 1,200 mg (n = 255) or placebo (n = 126) every 3 weeks for up to 24 months. Sequential and concurrent chemoradiation had been received by 34% and 66% of patients, respectively. PD-L1 expression data was unavailable for more than half of enrolled patients. The primary endpoint was progression-free survival on blinded independent central review.
Progression-Free Survival
At data cutoff for the interim analysis (March 2021), median follow-up was 14.3 months (interquartile range [IQR] = 6.4–19.4 months) for the sugemalimab group and 13.7 months (IQR = 7.1–18.4 months) for the placebo group. Median progression-free survival was 9.0 months (95% confidence interval [CI] = 8.1–14.1 months) in the sugemalimab group vs 5.8 months (95% CI = 4.2–6.6 months) in the placebo group (stratified hazard ratio [HR] = 0.64, 95% CI = 0.4–-0.85, P = .0026); 12-month rates were 45.4% vs 25.6%. Hazard ratios were 0.59 (95% CI = 0.39–0.91) among patients who had received sequential chemoradiation and 0.66 (95% CI = 0.44–0.99) among those who had received concurrent chemoradiation.
KEY POINTS
- Sugemalimab significantly prolonged progression-free survival vs placebo.
- At interim analysis, median progression-free survival was 9.0 vs 5.8 months.
Overall survival data were not mature at time of analysis. At data cutoff, death had occurred in 13% of patients in the sugemalimab group vs 25% of the placebo group.
Adverse Events
Grade 3 or 4 treatment-related adverse events occurred in 9% of the sugemalimab group vs 6% of the placebo group, most commonly pneumonitis or immune-mediated pneumonitis (3% vs < 1%). Treatment-related serious adverse events occurred in 15% vs 10% of patients, most commonly pneumonitis or immune-mediated pneumonitis in both groups (9% vs 7%). Grade 3 or 4 immune-mediated adverse events occurred in 4% of the sugemalimab group, most commonly pneumonitis (2%). Treatment-related death occurred in four patients (2%) in the sugemalimab group (due to pneumonia in 2 patients, pneumonia with immune-mediated pneumonitis in 1, and acute hepatic failure in 1) and in no patients in the placebo group.
The investigators concluded, “Sugemalimab after definitive concurrent or sequential chemoradiotherapy could be an effective consolidation therapy for patients with stage III NSCLC whose disease has not progressed after sequential or concurrent chemoradiotherapy. Longer follow-up is needed to confirm this conclusion.”
Yi-Long Wu, MD, of the Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by CStone Pharmaceuticals and the National Key Research and Development Program of China. For full disclosures of the study authors, visit thelancet.com.
