The efficacy of apelvis combined with fulvestrant in patients with PIK3CA mutant HR+/HER2- breast cancer

Alpelisib (Alpelisib), an oral and bioavailable PI3Kα selective inhibitor, has attracted widespread attention in the field of cancer treatment in recent years. Its safety and tolerability have been verified for the first time in patients with solid tumors carrying PIK3CA mutations, which lays the foundation for in-depth research on the potential of apelvis in the treatment of PIK3CA-mutated breast cancer.

In early preclinical studies, Apelvis has demonstrated good tolerability and therapeutic efficacy. In order to further explore its efficacy, the first human phase Ia clinical study was conducted. This study focused on the therapeutic effect and tolerability of apelvis in patients with advanced solid tumors with PIK3CA mutations. The study covered a variety of solid tumor types, with breast cancer accounting for the highest proportion. The results of the study showed that apelvis has a good safety profile at specific doses, and significant tumor responses were observed in some patients.

It is worth noting that the incidence of PIK3CA mutations is relatively high in HR+/HER2- breast cancer patients. Apelvis can increase estrogen receptor transcription in breast cancer cells by inhibiting PI3K activity. Therefore, a new therapeutic strategy is proposed: combining the PI3K inhibitor apelvis with endocrine therapy in order to achieve a more durable therapeutic response in PIK3CA-mutated HR+ breast cancer patients.

In a subsequent Phase Ib study, the combination of apelvis and fulvestrant was studied in postmenopausal women with PIK3CA-altered or wild-type HR+ metastatic breast cancer (MBC). The results of the study showed that in the patient group with PIK3CA alterations, treatment with apelvis combined with fulvestrant significantly prolonged progression-free survival (PFS), and the overall response rate was significantly higher than that in the wild-type group.

Based on the above research results, in order to further confirm the efficacy and safety of Apelvis, a large-scale phase 3 clinical study - SOLAR-1 study was carried out. This study aims to evaluate the efficacy and safety of apelvis combined with fulvestrant in PIK3CA mutant HR+/HER2- patients who have previously received endocrine therapy but not chemotherapy. The results of the study showed that compared with fulvestrant alone, apelvis combined with fulvestrant significantly prolonged the PFS of patients and improved the overall effective rate.

The positive results of the SOLAR-1 study provide strong support for the clinical application of Apelvis. Based on this, the U.S. Food and Drug Administration (FDA) officially approved apelvis combined with fulvestrant in May 2019 for the treatment of postmenopausal women and patients with HR+/HER2-, PIK3CA mutated advanced or metastatic breast cancer. At the same time, the FDA also approved Therascreen PIK3CA mutation detection to guide patient treatment selection. This test can accurately detect 80% of patients with known PIK3CA mutations, providing clinicians with a powerful basis for decision-making.