Combination of tucatinib and apelvis shows efficacy in patients with HER2-positive metastatic breast cancer

The combination of tucatinib and alpelisib showed promising efficacy in the treatment of patients with HER2-positive (HER2+) PIK3CA-mutated metastatic breast cancer (MBC), according to a study presented at the 2024 Breast Cancer Symposium. This study has attracted widespread attention because HER2-positive breast cancer is an aggressive disease that is often resistant to existing treatments, so finding new and effective treatment options is an important issue in the current field of oncology.

This Phase IB clinical trial used a time-to-event optimal interval design to determine the maximum tolerated dose of tucatinib and apelvis within a 28-day dose-limiting toxicity (DLT) window. Investigators used the Criteria for Cancer Treatment Evaluation (CTCAE v.5.0) to assess safety and strictly monitored all patients. This study focused on postmenopausal women or premenopausal women undergoing ovarian suppression who were diagnosed with HER2+ PIK3CA-mutated metastatic breast cancer and all had received at least two HER2-targeted therapies before receiving this treatment.

To date, the study has enrolled and treated eight patients with an average age of 53 years. These patients had received a variety of different MBC treatments before participating in the study, ranging from one to four treatments. Specifically, previous HER2-targeted therapies included trastuzumab and pertuzumab (8 patients in each group), T-DM1 (5 patients), tocatinib (4 patients), T-DXd (4 patients), and margetuximab (1 patient). Among these patients, 6 patients had visceral metastases, and 4 patients had central nervous system metastases.

The study results showed that all patients who experienced partial response (PR) carried the PIK3CA H1047R mutation. The researchers noted that these PRs usually occurred after two cycles of treatment and were accompanied by significant shrinkage of breast tumors, liver and lung metastases, and even observed regression of lymphatic spread of lung cancer. Among these 8 patients, 4 patients continued treatment for more than 6 months, with the longest treatment duration reaching 15 months and is still ongoing.

The researchers emphasized that the combination of tucatinib and apelvis was well tolerated at the first dose level (DL1), and 3 of the 5 evaluable patients experienced partial responses, for an overall response rate of 60%. This finding is particularly exciting because it included patients who had previously received tucatinib and T-DXd and were able to respond well to this combination.

Through this study, it can be seen that the combined application of tucatinib and apelvis can not only provide a new treatment option for patients with metastatic breast cancer with HER2-positive PIK3CA mutations, but also demonstrate its good tolerability and anti-tumor activity. This result lays the foundation for clinical practice and subsequent research. Further clinical trials will help verify the long-term efficacy and safety of this combination in a larger patient population.

References:https://www.docwirenews.com/post/the-combination-of-tucatinib-and-alpelisib-shows-efficacy-in-patients-with-her2-positive-metastatic-breast-cancer