Treatment-related adverse events in patients with advanced breast cancer receiving adjuvant AKT inhibitors: a meta-analysis of randomized controlled trials

Incorporation of AKT inhibitors into adjuvant therapy for advanced or metastatic breast cancer has improved clinical outcomes. However, the safety of AKT inhibitors should be better evaluated, given the possibility of prolonging survival and impacting patient quality of life. Our aim was to assess how the addition of AKT inhibitors to adjuvant therapy affects treatment-related adverse events.

We evaluated binary outcomes with risk ratios (RRs), with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I² statistics. R, version 4.2.3, was used for statistical analyses.

A total of seven RCTs comprising 1619 patients with BC. The adverse effects that show significance statistical favoring the occurrence of adverse effects in AKT inhibitor were diarrhea (RR 3.05; 95% CI 2.48–3.75; p < 0.00001; I² = 49%), hyperglycemia (RR 3.4; 95% CI 1.69–6.83; p = 0.00058; I² = 75%), nausea (RR 1.69; 95% CI 1.34–2.13; p = 0.000008; I² = 42%), rash (RR 2.79; 95% CI 1.49–5.23; p = 0.0013; I² = 82%), stomatitis (RR 2.24; 95% CI 1.69–2.97; p < 0.00001; I² = 16%) and vomiting (RR 2.99; 95% CI 1.85–4.86; p = 0.00009; I² = 42%). There was no significant difference between the groups for alopecia (p = 0.80), fatigue (p = 0.087), and neuropathy (p = 0.363380).

The addition of AKT inhibitors to adjuvant therapy was associated with an increase in treatment-related adverse events. These results provide safety information for further clinical trials evaluating AKT inhibitor therapy for patients with metastatic BC. Clinicians should closely monitor patients for treatment-related adverse events to avoid discontinuation of therapy and morbidity caused by these early-stage therapies.