A systematic review and meta-analysis of selected toxicity endpoints of alpelisib

Oncotarget. 2020 Oct 20;11(42):3793-3799. doi: 10.18632/oncotarget.27770.

Abstract

Purpose: Alpelisib is a first-in-class α-specific phosphatidylinositol 3-kinase inhibitor approved for the treatment of patients with estrogen receptor-positive metastatic breast cancer. High absolute risk (AR) of relevant toxicities has been observed with this treatment. This meta-analysis aimed to improve the precision of the estimated AR of selected adverse events (AEs) associated with this new agent.

Materials and methods: A literature search was conducted in August 2019 to identify trials analyzing the anti-tumor efficacy and toxicity profile of alpelisib. Heterogeneity was assessed by using I 2 statistics. Data were analyzed using random effect meta-analyses for AR. Eleven trials and 511 patients were included.

Results: There was no evidence of heterogeneity between studies regarding the AR of most AEs except for all-grade weight loss and grade 3-4 stomatitis. The number of serious AEs was clearly reported in only one study, of which the most common was hyperglycemia; the most common all-grade AEs were hyperglycemia (59%), diarrhea (56%), nausea (44%), and rash (38%). Grade 3/4 hyperglycemia and rash occurred in 28% and 10% of patients, respectively. No treatment-associated deaths were observed, and 18% of patients had to stop treatment due to toxicities.

Conclusions: Alpelisib is associated with clinically relevant AEs that can lead to treatment discontinuation. The most common AE was hyperglycemia. No treatment-related deaths were observed.

Keywords: adverse event; alpelisib; diarrhea; hyperglycemia; rash.

Publication types

  • Review