FIGHT Study Update Supports FGFR2-Targeted Treatment For Gastric, Gastro-oesophageal Cancer

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Updated progression-free survival (PFS) findings from the FIGHT study continue to favour the use of bemarituzumab alongside chemotherapy in patients with advanced gastric and gastro-oesophageal junction adenocarcinoma with fibroblast growth factor receptor (FGFR)2b overexpression. 

The results were presented at the 2021 ASCO Annual Meeting by Daniel Catenacci, from the University of Chicago in Illinois, USA, who said the monoclonal antibody targeting FGFR2b was previously reported to have a 17.9% partial response rate in the trial. 

The study included patients who had not previously been treated for locally advanced or metastatic disease and had FGFR2b overexpression and/or evidence of FGFR2 circulating tumour (ct)DNA amplification but without a confirmed HER2-positive status, he explained. 

Specifically, 83.2% of patients had a positive immunohistochemistry (IHC; 2+ or stronger staining) test finding but no ctDNA amplification whereas just 3.9% of patients were negative or unevaluable for FGFR2b overexpression but positive for ctDNA.  

The primary endpoint of PFS was a median 9.5 months for the 77 patients randomly assigned to receive bemarituzumab 15 mg/kg at 2-week intervals alongside a modified FOLFOX6 chemotherapy regimen every 2 weeks versus 7.4 months for the 78 patients who instead received placebo plus chemotherapy, giving a nonsignificant hazard ratio (HR) of 0.68. 

However, PFS analyses of patient subgroups with IHC 2+ expression in over 5% and over 10% of tumour cells significantly favoured bemarituzumab use, with HRs of 0.54 and 0.44, respectively. 

Overall survival (OS) was also significantly better with bemarituzumab plus FOLFOX6 versus placebo plus FOLFOX6, at a median of unreached versus 12.9 months and a HR of 0.58. The 5% and 10% tumour cell expression threshold subgroups again had improved HRs with bemarituzumab use, of 0.52 and 0.41, respectively.  

Subgroup analysis by age, sex, geographical region, prior use of neoadjuvant or adjuvant treatment, and receipt of FOLFOX6 before randomisation tended to favour bemarituzumab use, said Daniel Catenacci. 

And after a median follow-up of 12.5 months, there was a 5.7-month improvement in median OS between patients in the bemarituzumab arm versus controls (19.2 vs 13.5 months, HR=0.6), with the gain stronger in patients with greater than 5% and 10% tumour cell expression (HR=0.52 and 0.41, respectively). 

The objective response rate was 46.8% with bemarituzumab plus FOLFOX6 versus 33.3% with placebo, a difference of 13.1% in favour of the FGFR2b inhibitor’s use, with differences of 15.1% and 18.0% found for the 5% and 10% tumour expression subgroups, respectively, although none of these differences were statistically significant. 

The presenter noted that bemarituzumab was particularly associated with any-grade stomatitis (31.6 vs 13.0% with placebo) and dry eye (26.3 vs .5%). 

Corneal adverse events occurred in 67.1% of bemarituzumab-treated patients versus 10.4% controls, including grade 3 events in 23.7% versus 0.0%, but there were no grade 4 events in either group. Corneal side effects at grade 2–3 occurred after a median 23.7 and 12.8 months, respectively, and took a median of 19.1 and 2.0 weeks to resolve fully or to grade 1. 

“The delayed onset of corneal adverse events may allow an opportune time to intervene with prophylactic measures and this is being studied in future investigations”, he remarked. 

A phase III trial is now planned for the first-line treatment of FGFR2b-positive gastro-oesophageal cancer with bemarituzumab, the presenter concluded. 

Reference  

Catenacci DVT, Kang Y-K, Saeed A, et al. FIGHT: A randomized, double-blind, placebo-controlled, phase II study of bemarituzumab (bema) combined with modified FOLFOX6 in 1L FGR2b+ advanced gastric/gastroesophageal junction adenocarcinoma (GC). J Clin Oncol 2021;39(suppl 15; abstr 4010). DOI: 10.1200/JCO.2021.39.15_suppl.4010