Two studies led by researchers at The University of Texas MD Anderson Cancer Center demonstrated clinical benefit from novel targeted therapies, which may offer new treatment options for patients with metastatic hormone receptor–positive/HER2-negative breast cancer. The data were shared in oral presentations at the 2023 San Antonio Breast Cancer Symposium.
According to the National Cancer Institute, hormone receptor–positive/HER2-negative breast cancer is the predominant breast cancer subtype in the United States, comprising nearly 70% of all breast cancer cases. When caught at an early stage before it metastasizes, the disease is very treatable; however, the 5-year relative survival rate for metastatic hormone receptor–positive/HER2-negative breast cancer is only 34%, underscoring the need for innovative therapeutic approaches.
Futibatinib in Advanced Breast Cancer With FGFR1 Amplification
The phase II FOENIX-MBC2 trial, led by Senthil Damodaran, MD, PhD, Associate Professor of Breast Medical Oncology and Investigational Cancer Therapeutics at MD Anderson, achieved early signs of antitumor activity when combining the FGFR inhibitor futibatinib with the hormone therapy fulvestrant in patients with advanced hormone receptor–positive/HER2-negative breast cancer harboring high-level FGFR1 amplification (Abstract RF01-04).
Among 22 patients receiving the combination, the researchers observed a median progression-free survival of 7.2 months. The overall response rate was 18.2%, including four confirmed partial responses, and the median duration of response was 6.3 months.
“We are encouraged by the antitumor activity of futibatinib and the possibility of offering this targeted therapy to patients who have had their breast cancer progress after CDK4/6 inhibitor treatment,” Dr. Damodaran said. “We will continue to observe these patients and study further biomarkers of response.”
This open-label multicenter trial enrolled patients with locally advanced/metastatic breast cancer harboring FGFR gene amplifications who had progressed on prior CDK4/6 inhibitor treatment. Patients were enrolled in one of four treatment cohorts based on diagnosis and FGFR gene amplification status. Patients had a median age of 58 years, had received a median of three lines of any prior systemic anticancer therapy, and had all received previous CDK4/6 inhibitor treatment.
No treatment-related serious adverse events were reported. The most common treatment-related adverse events were hyperphosphatemia (in 95.5% of patients), alopecia (in 54.5%), constipation (in 45.5%), and dry mouth (in 40.9%).
Tinengotinib for Heavily Pretreated Metastatic Hormone Receptor–Positive/HER2-Negative or Triple-Negative Breast Cancers
Pooled data from two trials led by Sarina Piha-Paul, MD, Associate Professor of Investigational Cancer Therapeutics at MD Anderson, demonstrated clinical benefit with manageable side effects from tinengotinib, either alone or in combination with nab-paclitaxel, in heavily pretreated patients with metastatic hormone receptor–positive/HER2-negative or triple-negative breast cancers (Abstract RF01-07).
In 11 patients with hormone receptor–positive/HER2-negative breast cancer, tinengotinib monotherapy achieved an overall response rate of 45.5%, a clinical benefit rate of 64%, and a median progression-free survival of 5.68 months. The 17 patients with triple-negative breast cancer had an overall response rate of 23.5%, a clinical benefit rate of 29.4%, and a median progression-free survival of 2.73 months. Of note, partial responses were seen in three patients designated as HER2-zero and in two patients designated HER2-low.
"Tinengotinib has showcased clinical benefit for individuals facing refractory metastatic hormone receptor–positive/HER2-negative or triple-negative breast cancers, potentially elevating treatment outcomes," Dr. Piha-Paul said. "This positive impact was also observed among subgroups, including patients with HER2-zero and HER2-low disease."
The presentation pooled data from a phase I study and a phase Ib/II study. Among the 36 patients treated across both trials, 30 patients were treated with tinengotinib alone and 6 were treated with tinengotinib plus nab-paclitaxel. Twenty-eight patients receiving tinengotinib monotherapy were evaluated for efficacy. Patients had a median age of 51 years old and had received a median of five lines of prior therapy. All patients had no available standard treatment options.
No treatment-related serious adverse events were reported. The most common treatment-related adverse events seen with tinengotinib monotherapy were hypertension (in 60.0% of patients), stomatitis (in 50.0%), palmar-plantar erythrodysesthesia syndrome (in 46.7%), and diarrhea (in 20.0%). The most common treatment-related adverse events seen with tinengotinib in combination with nab-paclitaxel were decreased neutrophil count/neutropenia (in 50.0% of patients), stomatitis (in 50.0%), hypertension (in 33.3%), hyponatremia (in 33.3%), hypokalemia (in 33.3%), and nausea (33.3%). One patient on the combination had a grade 5 pulmonary hemorrhage.
Disclosure: The FOENIX-MBC2 trial was supported by Taiho Oncology, Inc.; Dr. Damodaran previously served on the Taiho advisory board. The pooled trial was supported by TransThera Sciences (Nanjing), Inc.; Dr. Piha-Paul reported research support from TransThera Bio.
