Addition of Bemarituzumab to Chemotherapy Improves Survival in Patients with FGFR2b-Positive Advanced Gastric Cancer

Bemarituzumab, an investigational first-in-class humanized immunoglobulin G1 monoclonal antibody that selectively binds to FGFR2b, improved progression-free survival (PFS) and overall survival (OS) when added to modified FOLFOX6 (mFOLFOX6) chemotherapy in patients with FGFR2b-positive advanced gastric or gastroesophageal junction (GEJ) cancer in the phase 2 FIGHT clinical trial.

These findings were reported by Zev A. Wainberg, MD, MSc, Co-Director, University of California, Los Angeles Gastrointestinal Oncology Program, at the virtual 2021 ASCO Gastrointestinal Cancers Symposium.

“The FIGHT study is the first study to evaluate targeting the overexpression of FGFR2b in any cancer and is the first randomized data set of any FGFR inhibitor in any malignancy,” Dr Wainberg said. “In our study, approximately 30% of patients had first-line non–HER2-positive gastric or GEJ adenocarcinoma overexpressing FGFR, using a centrally performed IHC [immunohistochemistry] test.”

Study Details

The global, randomized, FIGHT study included 155 patients with FGFR2b-positive advanced gastric or GEJ cancer. Researchers determined that approximately 95% of patients had FGFR2b overexpression based on IHC, and approximately 17% had FGFR2 amplification based on circulating tumor DNA. The median age of patients was 60 years, and 57% were of Asian descent.

Patients were randomized in a 1:1 ratio to 15 mg/kg bemarituzumab (N = 77) or placebo (N = 78) once every 2 weeks plus 1 additional dose of 7.5 mg/kg bemarituzumab or placebo on day 8. Approximately 45% of patients in each arm received a single dose of mFOLFOX6 before randomization. The study’s primary end point was investigator-assessed PFS. Secondary end points included OS, overall response rate (ORR), and frequency of adverse events.

Results showed an improvement in median PFS from 7.4 months in the placebo plus mFOLFOX6 arm to 9.5 months in the bemarituzumab plus mFOLFOX6 arm (hazard ratio [HR], 0.68; P = .0727), which was statistically significant, noted Dr Wainberg.

In addition, a positive correlation was observed between the benefit of bemarituzumab and the percentage of FGFR2b-positive tumor cells. For example, in patients with IHC 2+/3+ expression of FGFR2b ≥5%, the median PFS improved from 7.3 months in the placebo arm to 10.2 months in the bemarituzumab arm (HR, 0.54; 95% confidence interval [CI], 0.33-0.87). In those with IHC 2+/3+ expression ≥10%, the median PFS almost doubled, from 7.3 months to 14.1 months with the addition of bemarituzumab to mFOLFOX6 (HR, 0.44; 95% CI, 0.25-0.77).

“As FGFR2b overexpression increased, so too did the OS benefit in the patients who received bemarituzumab compared to placebo,” Dr Wainberg said.

In the overall study population, median OS was not reached in the bemarituzumab arm and was 12.9 months in the placebo arm (HR, 0.58; 95% CI, 0.35-0.95). In patients with IHC 2+/3+ expression ≥5%, the median OS was not reached in those who received bemarituzumab plus mFOLFOX6 and was 12.5 months in those who received placebo plus mFOLFOX6 (HR, 0.52; 95% CI, 0.31-0.91). In patients with IHC 2+/3+ expression ≥10%, the median OS was not reached in the bemarituzumab arm and was 11.1 months in the placebo arm (HR, 0.41; 95% CI, 0.22-0.79).

The ORR was 47% in the bemarituzumab plus mFOLFOX6 arm versus 33% in the placebo plus mFOLFOX6 arm. The median duration of response improved from 7.1 months with placebo to 12.2 months with bemarituzumab.

Safety Profile

The incidence of all-grade adverse events (AEs) was similar in the bemarituzumab and placebo arms (100% vs 98.7%, respectively). Ocular AEs, which are frequently associated with the use of therapies that target FGFR, were reported in the trial. Corneal AEs were more frequently observed in the bemarituzumab arm than in the placebo arm (67.1% vs 10.4%, respectively), with the most common of these events in the bemarituzumab arm being dry eye (26.3%), keratitis (15.8%), and punctate keratitis (14.5%).

In total, 34.2% of patients discontinued bemarituzumab therapy because of AEs compared with 5.2% of patients who received placebo. Of the 26 patients who discontinued bemarituzumab therapy, 21 did so because of an ocular AE.

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