FIGHT: Significant Improvement in Overall Survival Found in Patients with Advanced Gastric Cancer Treated with Bemarituzumab and Modified FOLFOX6

2021 Year in Review - Gastrointestinal Cancer

Statistically meaningful improvement in progression-free survival, overall survival, and objective response rate was found in patients with advanced gastric cancer treated with bemarituzumab and modified FOLFOX6.

Gastric cancer and gastroesophageal junction (GEJ) cancer are among the leading causes of cancer-related deaths worldwide, with low 5-year overall survival (OS) rates.1 Although current therapies improve survival, the recurrence rate is high. Palliative chemotherapy gives patients short-term benefits, with a median OS of 11 months.1 Various targeted therapies such as trastuzumab and pembrolizumab have proved beneficial in subgroups of patients with advanced gastroesophageal adenocarcinoma (GEA) who have tumors harboring molecular abnormalities.1 The amplification of the FGFR2 gene has been identified as conveying a worse prognosis in 5% to 10% of patients with GEA who harbor this errant gene.1 Bemarituzumab is a first-in-class humanized monoclonal antibody that blocks fibroblast growth factor ligands from binding to the FGFR2b receptor, thus inhibiting its action.1 It also mediates antibody-dependent cell-mediated cytotoxicity.1 In patients with refractory FGFR2b-positive gastric cancer, bemarituzumab monotherapy had a confirmed objective response rate (ORR) of 18% in patients in a phase 1 clinical trial.1

The FIGHT clinical trial is a phase 2 trial for patients with treatment-naïve unresectable locally advanced or metastatic gastric cancer that is HER2-negative and has centrally confirmed FGFR2b overexpression by immunohistochemistry (IHC) or FGFR2 amplification by circulating tumor DNA (ctDNA).1 Wainberg and colleagues presented results of this trial at the 2021 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. There were 910 patients evaluated, with 30% having FGFR2b-positive gastric cancer. Ultimately, 155 patients were randomized in the study, with 149 patients who were FGFR2b-positive by IHC and 26 by ctDNA.

Bemarituzumab was dosed at 15 mg/kg, as was a placebo. Doses were given every 2 weeks with an additional dose of 7.5 mg/kg bemarituzumab or placebo on day 8. Along with bemarituzumab or placebo, oxaliplatin plus leucovorin plus 5-fluorouracil (modified FOLFOX6) chemotherapy was administered to the trial’s patients. Treatment continued until the disease progressed or intolerable toxicity or death occurred. The study’s primary end point was progression-free survival (PFS), with secondary end points of OS, ORR, and adverse event (AE) frequency. PFS was 9.5 months for the group receiving bemarituzumab and 7.4 months for the placebo group. OS was 12.9 months for the placebo group. The median OS was not met for the group receiving bemarituzumab. In those patients who had measurable disease, the ORR improved by 40% in patients receiving placebo and 53% in patients treated with bemarituzumab. With increasing levels of FGFR2b expression there was an improved efficacy across PFS, OS, and ORR. Evaluation of AEs found 83% of patients receiving bemarituzumab and 74% receiving placebo reported grade ≥3 AEs. Serious AEs occurred in 32% of the bemarituzumab group and in 36% of the placebo group. Stomatitis and corneal AEs were more common in patients receiving bemarituzumab.

Bemarituzumab and modified FOLFOX6 therapy led to statistically meaningful PFS, OS, and ORR improvement.

Source: Wainberg Z, Enzinger P, Kang Y-K, et al. Randomized double-blind placebo-controlled phase 2 study of bemarituzumab combined with modified FOLFOX6 (mFOLFOX6) in first-line (1L) treatment of advanced gastric/gastroesophageal junction adenocarcinoma (FIGHT). J Clin Oncol. 2021;39(suppl_3):160-160.

Reference

  1. Catenacci DV, Tesfaye A, Tejani M, et al. Bemarituzumab with modified FOLFOX6 for advanced FGFR2-positive gastroesophageal cancer: FIGHT phase 3 study design. Future Oncol. 2019;15:2073-2082.
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