Futibatinib/Fulvestrant AEs Remains Consistent in Advanced FGFR+ Breast Cancer

The phase 2 FOENIX-MBC2 trial (NCT04024436) showed that futibatinib (Lytgobi; TAS-120) plus fulvestrant (Faslodex) demonstrated high and encouraging antitumor activity compared with futibatinib in patients with advanced/metastatic breast cancer harboring FGFR gene amplifications, according to Senthil Damodaran, MD, PhD.1

In a conversation with CancerNetwork® at the 2023 San Antonio Breast Cancer Symposium (SABCS), Damodaran, an assistant professor in the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center, discussed the adverse effects (AEs) associated with the combination regimen. While futibatinib/fulvestrant resulted in a median progression-free survival of 7.2 months (95% CI, 2.1-7.6) and a clinical benefit rate of 50% (95% CI, 28.2%-71.8%), it also resulted in increased levels of hyperphosphatemia. However, these AEs were consistent with the safety profiles for the agents, and no new AEs were found.

Frequent any-grade AEs included hyperphosphatemia (95.5%), alopecia (54.5%), constipation (45.5%), and dry mouth (40.9%). Additionally, grade 3 treatment-related AEs (TRAEs) were reported in 22.7% of patients; no grade 4 or 5 TRAEs were reported.

Transcript:

One of the things that happens when you target FGFR is that [patients’] phosphate levels go up, so they get hyperphosphatemia. That is an on-target effect of FGFR inhibitors. We saw that [during the trial], so that was one of the more common AEs that we saw in our treatment. As I said, this is a known on-target effect of specific FGFR1 inhibitors in clinical practice.

That's more of an alkaline abnormality. It is [fairly] treatable. Then we also saw a little bit of diarrhea and alopecia. Most of the safety signals were what we would expect with FGFR inhibition. I don't think we saw anything new or unexpected with the combination.

Reference

Damodaran S, Turner N, Krop I, et al. RF01-04 Final results from the phase 2, open-label FOENIX-MBC2 study: efficacy and safety of futibatinib in adult patients with locally advanced/metastatic HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification. Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Abstract RF01-04.