The FIGHT study’s invited discussant, Rutika Mehta, MD, MPH, a gastrointestinal oncologist at Moffitt Cancer Center, Tampa, Florida, noted the emergence of new biomarkers and their targeted agents in HER2-negative gastric or gastroesophageal junction cancer. Two important ones are FGFR2b—now targeted by bemarituzumab—and Claudin 18.2—targeted by zolbetuximab.
As Dr. Mehta noted, FGFR2 overexpression is seen in about 60% of gastric cancer cases; these tumors are associated with a higher tumor stage, lymph node metastasis, advanced stage, and poor prognosis. The 2b splice variant is expressed in up to 30% of gastric or gastroesophageal junction cancers. Bemarituzumab is a first-in-class humanized IgG1 monoclonal antibody specific to FGFR2b; it inhibits the ligand binding of FGF7, 10, and 22 and can enable antibody-dependent cell-mediated cytotoxicity.
Rutika Mehta, MD, MPH
Bemarituzumab was evaluated in the phase II FIGHT trial, which met its primary endpoint, progression-free survival, and also its key secondary endpoint, overall survival.1 Interestingly, Dr. Mehta noted, the Kaplan-Meier curves do not diverge until a few months after treatment initiation, which she called a “recurring theme” with chemotherapy/antibody combinations. “Response rates were also comparable to what we saw in the ToGA trial2 with chemotherapy and trastuzumab (47% vs 35% with chemotherapy alone), which is the only other targeted antibody used in gastric cancer,” she added. “As expected, higher expressors derived more benefit.”
Although efficacy is promising with bemarituzumab, there were some toxicities, noted Dr. Mehta, primarily stomatitis and ocular events. Corneal adverse events occurred in 67% of patients receiving bemarituzumab and were grade 3 in 24%. For 40% of patients, these side effects were still unresolved at the time of analysis. For others, the median time to resolution of these adverse events was about 7 months.
Dr. Mehta concluded that there is a “niche” for biomarker-directed therapies in the HER2-negative gastric or gastroesophageal junction space and maintained the results require further study. “A phase III study is warranted to confirm these findings in a larger population, with special attention paid to minimizing adverse events,” she commented.
DISCLOSURE: Dr. Mehta has received honoraria from Bristol Myers Squibb, Lilly, the National Comprehensive Cancer Network, Pfizer/EMD Serono, and Taiho Pharmaceutical; has served as a consultant or advisor to Bristol Myers Squibb and Taiho Pharmaceutical; and has been reimbursed for travel, accommodations, or other expenses by Bristol Myers Squibb.
1. Wainberg ZA, Enzinger PC, Kang YK, et al: Randomized double-blind placebo-controlled phase 2 study of bemarituzumab combined with modified FOLFOX6 in first-line treatment of advanced gastric/ gastroesophageal junction adenocarcinoma (FIGHT). 2021 Gastrointestinal Cancers Symposium. Abstract 160. Presented January 15, 2021.
2. Bang YJ, Van Cutsem E, Feyereislova A, et al: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet 376:687-697, 2010.
Gastric cancer appears to have a new druggable target: fibroblast growth factor receptor 2b (FGFR2b). Targeting FGFR2b with bemarituzumab plus chemotherapy led to clinically meaningful and statistically significant improvements in progression-free survival, overall survival, and response rate in...