Abstract / Summary
Background: Capivasertib is an oral pan-AKT inhibitor evaluated in combination with multiple systemic therapies across solid tumors, but its efficacy and safety vary by disease setting, biomarker status, and treatment backbone. We aimed to systematically evaluate the efficacy, safety, and early-phase clinical activity of capivasertib-containing combination regimens in advanced breast cancer and other solid tumors. Methods: MEDLINE, Web of Science, Scopus, Cochrane CENTRAL, trial registries, and major oncology conference sources were searched from inception to 31 May 2026. Randomized comparative studies, single-arm phase II studies, and phase I/Ib combination cohorts were included. Random-effects meta-analyses used restricted maximum likelihood estimation, with randomized and noncomparative evidence synthesized separately. Results: Twenty-seven reports representing 23 independent cohorts were included. In hormone receptor-positive/HER2-negative advanced breast cancer, capivasertib plus fulvestrant improved progression-free survival in the overall population (HR 0.59, 95% CI 0.51–0.69) and in PIK3CA/AKT1/PTEN-altered disease (HR 0.49, 95% CI 0.38–0.62), and increased objective response (RR 2.23, 95% CI 1.31–3.80). In triple-negative breast cancer, progression-free survival improved (HR 0.72, 95% CI 0.62–0.84), whereas overall survival remained inconclusive (HR 0.80, 95% CI 0.55–1.17). In PTEN-deficient metastatic hormone-sensitive prostate cancer, radiographic progression-free survival improved (HR 0.81, 95% CI 0.66–0.98). Capivasertib increased grade ≥ 3 adverse events (RR 1.66, 95% CI 1.06–2.60) and treatment discontinuation (RR 2.97, 95% CI 1.27–6.96). Conclusions: Capivasertib demonstrated disease-, biomarker-, and treatment backbone-specific activity, with the most consistent comparative benefit observed in hormone receptor-positive/HER2-negative advanced breast cancer. Increased toxicity should be considered when selecting patients and treatment combinations.