Sugemalimab Added to Chemotherapy Improves Survival, Response Rates for Patients With Advanced Esophageal Squamous Cell Carcinoma

Results From the Phase 3 GEMSTONE-304 Study

In a phase 3 study, the anti-PD-L1 monoclonal antibody, sugemalimab plus fluorouracil and cisplatin showed a significant and clinically meaningful improvement to progression-free survival (PFS), overall survival (OS), and objective response rate (ORR), for patients with advanced esophageal squamous cell carcinoma (ESSC), when compared to fluorouracil-cisplatin plus placebo.

These data were presented by Jin Li, MD, Fudan University Shanghai Cancer Center, Shanghai, China, at the 2023 World Congress on Gastrointestinal Cancers on June 28, 2023, in Barcelona, Spain.

The double-blinded phase 3 GEMSTONE-304 study randomized 540 patients with advanced ESSC on a 2-to-1 basis to receive fluorouracil-cisplatin every 3 weeks for up to 6 cycles, plus either 1200 mg of intravenous sugemalimab (n = 358) or placebo (n = 182) every 3 weeks for up to 24 months. Patients were stratified by PD-L1 expression status, ECOG performance status, and distant metastasis. The primary end points were PFS as determined by a blinded independent central review and OS in the intent-to-treat population. Secondary endpoints included PFS as assessed by investigator, ORR, duration of response (DoR), and safety.

At the data cutoff date of October 7, 2022, the median follow-up duration was 15.2 months. The PFS as assessed by blinded independent central review demonstrated a statistically significant improvement in the sugemalimab arm (median PFS, 6.2 months) compared with the placebo arm (5.4 months; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.54 to 0.82; P = .0002). The median overall survival in the sugemalimab arm was 15.3 months vs 11.5 months in the placebo arm (HR, 0.70; 95% CI, 0.55 to 0.90; P = .0076). These benefits were seen across all pre-specified subgroups. There was also a significantly higher ORR in the sugemalimab arm (60.1%) compared with the placebo arm (45.2%) and more durable response (median DoR 6.0 months vs 4.5 months).

There were comparable rates of grade≥3 treatment-related adverse events (51.3% vs 48.4%), serious treatment-related adverse events (21.5% vs 13.2%), discontinuation due treatment-emergent adverse events (13.3% vs 10.4%), and deaths due to treatment-related adverse events (1.7% vs 0.5%) between the sugemalimab and placebo arms.

Dr Li and coauthors concluded “These results support the use of [sugemalimab plus fluorouracil-cisplatin] as [first-line] treatment for unresectable locally advanced, recurrent or metastatic ESCC.”

Source:

Li J, Chen Z, Bai Y, et al. GEMSTONE-304: A phase 3 study of sugemalimab plus chemotherapy versus chemotherapy as first-line treatment of patients with unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC). Presented at the World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract O-4