Adding bemarituzumab to standard chemotherapy improves overall survival (OS) in patients with FGFR2b-expressing advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to phase 2 results published in The Lancet Oncology.
These results, from the FIGHT trial, also showed no significant improvement in progression-free survival (PFS) with bemarituzumab.
The FIGHT trial (ClinicalTrials.gov Identifier: NCT03694522) included 155 patients with HER2-negative, FGFR2b-selected advanced gastric or GEJ adenocarcinoma. At baseline, the median age of the cohort was 60 years, 72% of patients were men, and 57% were Asian.
Patients were randomly assigned to receive bemarituzumab (n=77) or placebo (n=78), each in combination with modified 5-fluorouracil, leucovorin, and oxaliplatin. In both arms, 99% of patients received their assigned treatment.
The primary endpoint was PFS. At a median follow-up of 10.9 months, PFS was not significantly different between the treatment arms. The median PFS was 9.5 months with bemarituzumab and 7.4 months with placebo (hazard ratio [HR], 0.68; 95% CI, 0.44-1.04; P =.073).
Similarly, the objective response rate was not significantly different between the treatment arms — 47% in the bemarituzumab arm and 33% in the placebo arm (P =.11). The median duration of response was 12.2 months with bemarituzumab and 7.1 months with placebo.
However, the median OS was significantly longer in the bemarituzumab arm than in the placebo arm — not reached and 12.9 months, respectively (HR, 0.58; 95% CI, 0.35-0.95; P =.027). In a post hoc analysis with a median follow-up of 12.5 months, the median OS was 19.2 months with bemarituzumab and 13.5 months with placebo (HR, 0.60; 95% CI, 0.38-0.94).
The most common grade 3 or higher adverse events (AEs; in the bemarituzumab and placebo arms, respectively) were a decrease in neutrophil count (30% vs 35%), cornea disorders (24% vs 0), neutropenia (13% vs 9%), stomatitis (9% vs 1%), and anemia (8% vs 13%).
Corneal AEs of any grade occurred in 67% of patients in the bemarituzumab arm and 10% of those in the placebo arm. The most common corneal AE was dry eye (26% and 6%, respectively). Corneal AEs resolved in 45% of patients in the bemarituzumab arm and 25% of those in the placebo arm. The median time to resolution was 23.1 weeks and 1.4 weeks, respectively.
The researchers noted that FIGHT “is the largest trial of any FGFR inhibitor reported to date in any cancer and provides the first randomized data of an FGFR inhibitor.”
“Although bemarituzumab was not superior to placebo for the outcome of progression-free survival in patients with FGFR2b-selected advanced gastric or gastroesophageal junction adenocarcinoma, findings from this study indicate that bemarituzumab might meaningfully improve progression-free survival and overall survival in patients with an overexpression of FGFR2 in at least 5% or 10% of tumor cells, and so further assessment is needed in this population,” the researchers concluded.
Disclosures: This study was supported by Five Prime Therapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Wainberg ZA, Enzinger PC, Kang Y-K, et al. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): A randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. Published online October 13, 2022. doi:10.1016/S1470-2045(22)00603-9