Adding bemarituzumab to chemo may up survival in advanced FGFR2b+, HER2- gastric cancer

Adding bemarituzumab to mFOLFOX6 significantly improved survival outcomes and response rate compared with mFOLFOX6 alone in patients FGFR2b-positive, HER2-negative gastric cancer, according to the FIGHT study presented at the 2021 ASCO GI Cancer Symposium. 

Bemarituzumab is a first-in-class humanized monoclonal antibody that selectively targets the FGFR2b receptor, commonly found to be overexpressed in gastric cancer patients (up to 60 percent).

“The FIGHT trial is the first study to evaluate targeting the overexpression of FGFR2b in any cancer and is the first randomized dataset of any FGFR2b inhibitor in any malignancy,” said lead investigator Dr Zev Wainberg from the University of California, Los Angeles in in Los Angeles, California, US.

Originally designed as a phase III study with target participants of 550 patients, the double-blind FIGHT study was later changed to a proof-of-concept phase II trial after enrolment of 155 patients with unresectable locally advanced or metastatic FGFR2b+, HER2- gastric cancer. [ASCO GICS 2021, abstract 160]

Among 910 patients prescreened for FGFR2b status, 30.2 percent showed FGFR2b overexpression and/or FGFR2 gene amplification. Of these 275 individuals, 155 were eventually randomized to 1:1 to frontline mFOLFOX6 with or without bemarituzumab 15 mg/kg Q2W*. The patients continued treatment until their disease had progressed, experienced intolerable toxicity, or death.

The primary outcome of median progression-free survival (PFS) was 9.5 months with the addition of bemarituzumab compared with 7.4 months with mFOLFOX6 alone. The corresponding hazard ratio (HR) was 0.68 (p=0.0727), which met the predefined criteria of HR ≤0.76 and p≤0.2 for statistical significance. 

Patients treated with bemarituzumab + mFOLFOX6 also had significantly longer overall survival (OS) than those receiving mFOLFOX6 alone (median, not reached vs 12.9 months; HR, 0.58; p=0.0268).

The survival benefit with bemarituzumab became more prominent with higher levels of FGFR2b overexpression: HRs of PFS were 0.68, 0.54, and 0.44 for the ITT population, those with FGFR2b expression ≥5 percent, and FGFR2b expression ≥10 percent, respectively. Similar findings were seen for OS, whereby HRs were 0.58, 0.52, and 0.41 for the respective subgroups.

“The FIGHT study is the first study to demonstrate that biomarker selection exists beyond HER2,” session discussant Dr Rutika Mehta from the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, US.

While the results were promising, Mehta also noted that certain adverse events (AEs), such as corneal AEs (67.1 percent vs 10.4 percent) and stomatitis (31.6 percent vs 13.0 percent), occurred more frequently in the bemarituzumab group than the mFOLFOX6 group.

“A phase III study is warranted to confirm the findings in a larger population, with special attention being paid to minimizing adverse events of bemarituzumab,” she said.

“The FIGHT results support a prospective randomized phase III study in gastric and gastroesophageal adenocarcinoma, and the evaluation of bemarituzumab in other FGFR2b-positive tumour types,” agreed Wainberg.

*with 1 additional 7.5mg/kg bemarituzumab dose on day 8 for bemarituzumab arm