Abstract
In the phase II FIGHT trial, adding bemarituzumab to chemotherapy led to longer progression-free survival and overall survival in patients with advanced FGFR2b-positive gastric or gastroesophageal junction cancers. However, the agent was also associated with more side effects, including eye problems.
Adding bemarituzumab (FPA144; Five Prime) to chemotherapy may improve survival for patients with advanced FGFR2b-positive gastric or gastroesophageal junction (GEJ) cancers, researchers reported at the American Society of Clinical Oncology 2021 Gastrointestinal Cancers Symposium, held virtually January 15–17 (J Clin Oncol 2021;39, no. 3_suppl. 160). In the phase II FIGHT trial, the combination led to longer progression-free survival (PFS) and overall survival (OS) compared with chemotherapy alone, although it was associated with more side effects.
FGFR2b is overexpressed in various cancers, including up to 61% of gastric cancers. Bemarituzumab is a targeted antibody designed to inhibit FGFR2b on tumor cells, thus blocking growth factor signaling. In a phase I trial, bemarituzumab monotherapy elicited responses in 18% of patients with advanced FGFR2b-positive gastric cancer (J Clin Oncol 2020;38:2418–26). These results led researchers to test the agent in a phase II trial.
The FIGHT trial enrolled 155 patients with locally advanced or metastatic gastric or GEJ cancer who were not eligible for surgery. All patients had FGFR2b overexpression and/or FGFR2 gene amplification and were HER2 negative. Patients received either bemarituzumab plus standard chemotherapy or chemotherapy alone.
Patients treated with the combination had a median PFS of 9.5 months and a response rate of 47% and did not reach median OS, compared with 7.4 months, 33%, and 12.9 months, respectively, in patients who received chemotherapy alone. “Importantly, as increased levels of FGFR2b overexpression were seen, so too was benefit seen in the group of patients who received bemarituzumab,” noted Zev Wainberg, MD, of the University of California, Los Angeles, who presented the results.
Adverse events classified as grade 3 or higher occurred in 82.9% of patients in the bemarituzumab group and 74% of patients in the control group. Notably, 67.1% of patients treated with bemarituzumab experienced corneal side effects—most commonly dry eye and inflammation—compared with 10.4% of patients in the control group.
“This was interesting data, and we were excited to see it. For a phase II trial, it's very robust,” said Yelena Janjigian, MD, of Memorial Sloan Kettering Cancer Center in New York, NY, who was not involved. She said that researchers should test the combination in a phase III trial with a broader patient population and further investigate the corneal side effects.
Janjigian noted that patients with gastric or GEJ cancer have had more treatment options in recent years, in part due to the success of immune checkpoint inhibitors. If bemarituzumab is approved, “then the devil will be in identifying populations that are most likely to benefit from anti–PD-1 versus FGFR2 inhibition,” she said.
Crystal Denlinger, MD, of Fox Chase Cancer Center in Philadelphia, PA, who wasn't connected to the trial either, considers the findings clinically meaningful—although the corneal side effects will necessitate ophthalmologic assessments throughout treatment. The trial provides further evidence that “gastric cancer is no longer one disease, but rather a number of disease subtypes that may ultimately require different targeted approaches,” she said. Thus, patients diagnosed with advanced disease should be tested for various biomarkers to determine the most suitable treatment.
“Gastric cancer is seeing an explosion of new therapies,” Denlinger added, yet survival is still limited for most patients with advanced disease. “The FIGHT study suggests that [FGFR inhibitors] may be an additional tool in our armamentarium, expanding treatment options and ultimately getting closer to our goal of personalizing cancer care.” –Catherine Caruso
