In the phase II FIGHT trial reported in The Lancet Oncology, Zev A. Wainberg, MD, and colleagues found numerically better progression-free survival with the addition of the anti-FGFR2b antibody bemarituzumab to mFOLFOX (modified fluorouracil, leucovorin, and oxaliplatin) in patients with HER2-nonpositive (ie, negative, indeterminate, borderline, or unknown), FGFR2b-selected advanced gastric or gastroesophageal junction adenocarcinoma.
Zev A. Wainberg, MD
The double-blind trial included 155 patients with tumor FGFR2b overexpression recruited from sites in 17 countries. Overall, 57% of patients were Asian. Patients could not be candidates for curative therapy and could not have received previous treatment with any selective inhibitor of the FGF-FGFR pathway.
They were randomly assigned between November 2017 and May 2020 to receive bemarituzumab at 15 mg/kg (n = 77) or placebo (n = 78) every 2 weeks with mFOLFOX6 given with oxaliplatin at 85 mg/m², leucovorin at 400 mg/m², and fluorouracil at 400 mg/m² bolus followed by infusion of 2,400 mg/m² over 46 hours every 2 weeks.
The primary endpoint was investigator-assessed progression-free survival.
Median follow-up was 10.9 months (interquartile range = 6.3–14.2 months). Median progression-free survival was 9.5 months (95% confidence interval [CI] = 7.3–12.9 months) in the bemarituzumab group vs 7.4 months (95% CI = 5.8–8.4 months) in the placebo group (hazard ratio [HR] = 0.68, 95% CI = 0.44–1.04, P = .073).
Median progression-free survival was 10.2 vs 7.3 months (HR = 0.54, 95% CI = 0.33–0.87) among 118 patients with FGFR2b overexpression in ≥ 5% of tumor cells and 14.1 vs 7.3 months (HR = 0.44, 95% CI = 0.25–0.77) among 96 with overexpression in ≥ 10% of tumor cells.
At the time of analysis (data cutoff in September 2020), median overall survival was not reached (95% CI = 13.8 months to not reached) in the bemarituzumab group vs 12.9 months (95% CI = 9.1–15.0 months) in the placebo group (HR = 0.58, 95% CI = 0.35–0.95, P = .027). In post hoc analysis with additional follow-up (data cutoff in February 2021), median overall survival was 19.2 months (95% CI = 13.6 months to not reached) vs 13.5 months (95% CI = 9.3–15.9 months, HR = 0.60, 95% CI = 0.38–0.94).
Grade ≥ 3 adverse events occurred in 83% of patients in the bemarituzumab group vs 74% of the placebo group, with common events consisting of decreased neutrophils (30% vs 35%), cornea disorder (24% vs 0%), neutropenia (13% vs 9%), stomatitis (9% vs 1%), and anemia (8% vs 13%). Any-grade corneal adverse events occurred in 67% vs 10% of patients.
Serious adverse events occurred in 32% vs 36%. Treatment was discontinued due to adverse events in 54% vs 36% of patients. Treatment-related death occurred in three patients in the bemarituzumab group (due to sepsis in two and pneumonia in one) and no patients in the placebo group.
The investigators concluded, “In this exploratory phase II study, despite no statistically significant improvement in progression-free survival, treatment with bemarituzumab showed promising clinical efficacy. Confirmatory phase III trials of bemarituzumab plus mFOLFOX6 powered to demonstrate statistical significance are being investigated in patients with previously untreated, FGFR2b-overexpressing, advanced gastric or gastroesophageal junction adenocarcinoma.”
Dr. Wainberg, of the Department of Medicine, University of California Los Angeles Medical Center, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Five Prime Therapeutics. For full disclosures of the study authors, visit thelancet.com.
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