Dr Damodaran on Futibatinib Plus Fulvestrant in FGFR1-Amplified HR+/HER2– Breast Cancer

Senthil Damodaran, MD, PhD, associate professor, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the efficacy of futibatinib (Lytgobi) plus fulvestrant (Faslodex) in patients with 

-amplified metastatic hormone receptor (HR)–positive, HER2-negative breast cancer according to findings from the phase 2 FOENIX-MBC2 trial (NCT04024436).

The phase 2, open-label, signal-seeking study assessed the efficacy and safety of futibatinib alone or in combination with fulvestrant in adult patients with locally advanced/metastatic HR-positive, HER2-negative breast cancer who harbored 

 gene amplification, Damodaran begins. The study included 4 patient cohorts, one of which enrolled 22 patients with high-level 

 amplification. All of these patients had previously received a CDK4/6 inhibitor and experienced disease progression on a different prior therapy. Patients in this arm had received a median number of 2.5 prior lines, including neoadjuvant therapies.

Final results from this cohort of patients treated with the combination regimen were presented at the 

. Futibatinib plus fulvestrant produced 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%), he reports. The agent also produced a partial response rate of 18.2% (95% CI, 5.2%-40.3%), stable disease in 50% of patients, and disease progression in 27.3% of patients. The median duration of response was 6.3 months (95% CI, 3.3-16.7).

Overall, futibatinib and fulvestrant demonstrated high and encouraging antitumor activity in this patient population, Damodaran reports. Notably, the regimen's activity is comparable with historical data for fulvestrant alone in the post-CDK4/6 inhibitor setting. Future research is needed to elucidate the benefit of futibatinib for patients with HR-positive, HER2-negative breast cancer, he concludes.

Videos

Senthil Damodaran, MD, PhD, discusses the efficacy of futibatinib plus fulvestrant in patients with FGFR1-amplified metastatic hormone receptor–positive, HER2-negative breast cancer according to findings from the phase 2 FOENIX-MBC2 trial.

Senthil Damodaran, MD, PhD, associate professor, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the rationale for the phase 3 ELAINE-3 trial (NCT05696626) in patients with estrogen receptor (ER)–positive, HER2-negative metastatic breast cancer harboring 

ELAINE-3 will enroll patients with ER-positive, HER2-negative breast cancer with 

 mutations. Several platforms can identify 

 mutations in circulating tumor DNA, Damodaran says. The earlier phase 2 ELAINE-1 (NCT03781063) and ELAINE-2 (NCT04432454) trials tested for 

 mutations using a smaller panel with approximately 6 genes, Damodaran notes.

The ELAINE-3 trial is using the Guardant360

 CDx liquid biopsy next generation sequencing–based test, which was approved by the FDA on January 30, 2023, as a companion diagnostic for patients with 

-mutant, ER-positive, HER2-negative advanced or metastatic breast cancer. This is a broad panel that sequences for alterations in 90 genes, so although the ELAINE-3 investigators will focus on finding 

 mutations, the assay results will provide supplemental information about additional genes, Damodaran explains.

Dr Damodaran on Lasofoxifene Plus Abemaciclib in ELAINE-2 and ELAINE-3

The ELAINE-3 trial is supported by findings from the single-arm phase 2 ELAINE-2 trial, which investigated the efficacy and safety of lasofoxifene plus abemaciclib (Verzenio). The ELAINE-2 investigators hypothesized that patients with ER-positive, HER2-negative metastatic breast cancer with 

 mutations may derive more benefit from combination regimens than monotherapies, Damodaran says. Since lasofoxifene-containing combinations had shown preclinical activity in patients with 

 mutations, the investigators decided to combine lasofoxifene with other agents, Damodaran notes. Preclinical studies at institutions such as The University of Texas MD Anderson Cancer Center showed that abemaciclib is still active in patients who had have previously progressed on CDK4/6 inhibitors such as palbociclib (Ibrance) and ribociclib (Kisqali), according to Damodaran.

Based on these preclinical data, ELAINE-2 investigated the combination of lasofoxifene and abemaciclib, the findings from which were presented at the 2022 ASCO Annual Meeting. ELAINE-2 evaluated the safety of the combination and demonstrated a median progression-free survival of 13.9 months with the regimen, which is not typically expected in patients who have progressed on prior CDK4/6 inhibitors, Damodaran explains. As ELAINE-2 was a small trial, its findings need to be confirmed in the larger, randomized ELAINE-3 trial, in which the investigational combination of lasofoxifene plus abemaciclib is being compared with standard-of-care fulvestrant (Faslodex) plus abemaciclib, Damodaran concludes.

Senthil Damodaran, MD, PhD, discusses the rationale for the phase 3 ELAINE-3 trial in patients with estrogen receptor–positive, HER2-negative metastatic breast cancer harboring ESR1 mutations.

Dr Damodaran on the ELAINE-3 Trial in Patients With ESR1-Mutated ER+/HER2– Metastatic Breast Cancer

Senthil Damodaran, MD, PhD, assistant professor, Department of Breast Medical Oncology, Division of Cancer Medicine, the University of Texas MD Anderson Cancer Center, discusses the phase 2 ELAINE-2 trial (NCT04432454). 

In the trial, investigators evaluated the safety and efficacy of lasofoxifene in combination with abemaciclib (Verzenio) in patients with locally advanced or metastatic 

-mutated, estrogen receptor (ER)–positive/HER2-negative metastatic breast cancer.

Efficacy data presented at the 2022 ASCO Annual Meeting showed that the censored median progression-free survival (PFS) achieved with the regimen was 13 months (95% CI, 32.0 weeks–not estimable). Of the 29 patients who were enrolled to the trial, 12 remained on treatment at the time of the presentation, Damodaran says.

Moreover, the objective response rate (ORR) achieved with the doublet was 50% (95% CI, 29.0%-71.0%). Damodaran explains that this percentage is notable, since 96.6% of enrolled patients previously received a CDK4/6 inhibitor, 79.3% received prior fulvestrant (Faslodex), and 48.3% received prior chemotherapy in the metastatic setting.

Given the prior treatment received by patients who participated in ELAINE-2, the PFS and ORR benefits provided with the combination of lasofoxifene plus abemaciclib are promising for this patient population, Damodaran concludes.

Senthil Damodaran, MD, PhD, discusses data from the phase 2 ELAINE-2 trial examining the combination of lasofoxifene and abemaciclib in patients with ESR1-mutated, estrogen receptor–positive/HER2-negative metastatic breast cancer.

Senthil Damodaran, MD, PhD

Articles

Dr Damodaran on Futibatinib Plus Fulvestrant in FGFR1-Amplified HR+/HER2– Breast Cancer

Dr Damodaran on the ELAINE-3 Trial in Patients With ESR1-Mutated ER+/HER2– Metastatic Breast Cancer

Dr. Damodaran on the ELAINE-2 Trial of Lasofoxifene/Abemaciclib in ESR1-Mutated, ER+/HER2- Breast Cancer