Introduction: Phosphatidylinositol 3-Kinase (PI3K) inhibitors are emerging as promising therapeutic agents for the treatment of breast cancer. Fatigue and nausea are prevalent adverse effects associated with cancer therapy. Therefore, we performed a meta analysis to elucidate the Relative Risks (RRs) of fatigue and nausea attributable to PI3K inhibitors.

Methods: Databases were searched for articles published until December 2024 reporting on phase II/III randomized controlled trials. Summary proportions and RRs for all-grade and grade 3/4 events were computed using either random-or common-effects models.

Results: We included 11 trials. There were 2427 patients with BC who received PI3K inhibitors, and 2061 received placebos. The RR for all-grades and grade 3/4 fatigue was 1.25 and 2.38, respectively. The RR of all-grade nausea was 1.73 (95% Confidence Interval [CI]). In subgroup analyses, Alpelisib significantly increased the risk of grade 3/4 nausea, and the risk of fatigue and nausea was lower in patients with Human Epidermal Growth Factor Receptor 2 (HER2) (+) BC than in those with HER2 (-) BC. The FDA Adverse Event Reporting System (FAERS) database showed that the Reporting Odds Ratios (RORs) for fatigue and nausea were 2.281 and 2.003, respectively.

Conclusion: Treatment with PI3K inhibitors increased the risk of fatigue and nausea. Given their significant impact on quality of life, early identification and appropriate management are crucial for optimizing overall treatment outcomes.