Research progress of Alpelisib in the treatment of endometrial cancer

Alpelisib - Piqray, a small molecule targeted inhibitor of the PI3Kα pathway, was initially approved for HR-positive, HER2-negative advanced breast cancer with PIK3CA mutations. However, in recent years, its potential in the treatment of endometrial cancer has received increasing attention. The pathogenesis of endometrial cancer is complex. Abnormal activation of the PI3K/AKT/mTOR signaling pathway plays a key role in the occurrence and progression of endometrial cancer. This makes PI3Kα selective inhibitors such as apelvis an important research focus. Therapeutic strategies targeting this target aim to provide new treatment options for patients by blocking abnormal signaling, inhibiting tumor cell proliferation and promoting apoptosis.

Multiple phase II studieshave shown that apelvis exhibits considerable anti-tumor activity in patients with PIK3CA-mutated endometrial cancer. In some studies, the overall response rate reached 71%, indicating that most patients experienced a significant reduction in tumor burden after treatment. This data, although from an early-stage study, provides preliminary evidence for the potential use of Apelvis in endometrial cancer. In addition, the study also observed that apelvis can improve patients' quality of life indicators, such as pain reduction and improvement in performance status, which is particularly important for patients with advanced endometrial cancer, because their long-term quality of life is often affected by tumor symptoms and traditional treatment side effects.

Despite encouraging preliminary efficacy, apelvis has not been approved for endometrial cancer indications, mainly due to limited sample size, insufficient long-term follow-up data, and validation of efficacy and safety is still in progress. Current research is still focused on early clinical trials, and more randomized controlled studies are needed in the future to confirm its long-term benefits and safety. In addition, Apelvis's research on endometrial cancer also emphasizes the importance of precision medicine, that is, the targeted effect of the drug is most significant only in patients with clear PIK3CA mutations, which further promotes the development of personalized treatment.

Reference materials:https://www.gynecologiconcology-online.net/article/S0090-8258(24)00139-2/fulltext