What is the clinical effect of Apelvis?

Alpelisib (Alpelisib) is an oral PI3K inhibitor that is effective in tumors with PIK3CA mutations, especially in combination with fulvestrant, and is commonly used to treat breast cancer. It inhibits the growth and proliferation of tumor cells by targeting the PI3K signaling pathway, thereby achieving the effect of treating cancer. Two major studies investigated the efficacy and safety of adding apelvis to pretreated patients with HR+HER2- advanced breast cancer (ABC).

In the phase 3 SOLAR-1 trial, 571 patients with HR+HER2-ABC (i.e., with and without PIK3CA-mutated tumors in 2 independent cohorts) who had previously received endocrine therapy (ET) (572 total, but 1 had never received treatment) were given fulvestrant plus apelix/placebo. In patients with PIK3CA mutations in tumor tissue (n=341), the addition of apelvis can significantly prolong PFS (apelix + fulvestrant is 11.0 months, while placebo + fulvestrant is 5.7 months, p<0.001), improve the overall response (OR) rate ( 26.6% vs. 12.8%), and increased overall survival (OS) (39.3 months vs. 31.4 months), but not statistically significantly. In patients without PIK3CA mutations, apelvis did not significantly affect progression-free survival (PFS) and overall response (OR).

However, in the PIK3CA mutant cohort of the SOLAR-1 trial, only 5.3% of patients treated with apelvis received CDK4/6i pretreatment, which is the current standard of care. The ongoing phase 2 BYLieve trial is evaluating apelix and ET in patients with HR+HER2-PIK3CA mutated ABC who have progressed on prior therapy. Patients were divided into 3 groups according to previous treatment: previous CDK4/6i + aromatase inhibitor (AI), previous CDK4/6i + fulvestrant, and previous ET or chemotherapy. The first results from the previous CDK4/6i+AI cohort showed a median PFS of 7.3 months, with 50.4% of patients progression-free after 6 months. Thus, Apelvis appears to have meaningful efficacy even after prior CDK4/6i treatment.

Both trials reported controllable toxicities of apelix. Common side effects may include nausea, vomiting, diarrhea, rash, etc. The observed side effects can be controlled through early intervention, adequate supportive measures, treatment interruption and dose reduction.

The consistent and significant results of these 2 trials led the U.S. Food and Drug Administration (FDA) to Approved in May 2019Apelix for the treatment of advanced breast cancer patients with HR+HER2-PIK3CA mutations. Authorized by the European Medicines Agency (EMA) in July 2020. Becauseapelix has been approved for a relatively short period of time, real-world data on its toxicity and therapeutic management are limited.