Potential Combination Regimens With Fulvestrant in HR+/HER2− Breast Cancer

Following results from the phase 2 FOENIX-MBC2 trial (NCT04024436), assessing futibatinib (TAS-120; Lytgobi) and futibatinib plus fulvestrant (Faslodex) in patients with advanced/metastatic breast cancer harboring FGFR gene amplifications, Senthil Damodaran, MD, PhD, discussed potential future directions with the fulvestrant including combining it with other agents.

In an interview with CancerNetwork® during the 2023 San Antonio Breast Cancer Symposium (SABCS), Damodaran, assistant professor in the department of breast medical oncology at the University of Texas MD Anderson Cancer Center, indicated that there may be benefit in combining the agent with a selective estrogen receptor modulator (SERM) and a selective estrogen receptor degrader (SERM).

Transcript:

We want to see if there's an opportunity to [assess] other novel SERMs and SERDs that are being evaluated in clinical trials because, in some sense, we also want to see how the response is with the novel agents that could still have activity after prior fulvestrant. For this study, since we know that was being done in combination with fulvestrant, we excluded patients who have [received] fulvestrant. However, in practice, it's likely that many of these patients would have received fulvestrant. We want to see if adding novel SERMs or SERDs with an FGFR inhibitor would lead to better clinical response. In some sense, that would be the next step or progression before we look at larger clinical studies.

Incidentally, I know this was not part of the presentation. When we did the FOENIX-MBC2 study, we had 4 different cohorts. The one that we presented was cohort 4, which was basically [patients with] hormone receptor–positive breast cancers with measurable disease. We [administered] fulvestrant plus futibatinib. We also had cohorts where we treated patients with triple-negative breast cancer with FGFR2 amplifications with single-agent futibatinib. FGFR2 amplification is a little bit different than FGFR1. We tend to see FGFR1 in hormone receptor–positive breast cancers. We tend to see FGFR2 amplifications in triple-negative breast cancers. In that group, patients don't necessarily need a hormone blocking agent as a partner. The HR-positive group would require something like fulvestrant or a SERD, but for triple-negative breast cancer, we administer an FGFR inhibitor. That was presented as a poster at SABCS.

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.