Efficacy and safety analysis of AKT inhibitor in triple-negative breast cancer: A meta-analysis and systematic review

Abstract

Objective: To determine the clinical benefit of monotherapy with AKT inhibitors in patients diagnosed with triple-negative breast cancer (TNBC). Methods: A systematic search was conducted in PubMed, Embase, and Cochrane Library for articles reporting treatment with AKT inhibitors in TNBC. The primary endpoint was progression-free survival and overall survival (OS). Secondary endpoints included the clinical benefit rate (CBR, included the proportion of patients with complete response, partial response, and stable disease), overall response rate (ORR, included the proportion of patients with complete response and partial response), all drug-related adverse events (AEs), and ≥3 grade drug-related grade AE. Results: We included 723 patients from 5 studies and observed a pooled progression-free survival of 0.80 (95% CI: 0.62–1.02; The Grading of Recommendations, Assessment, Development, and Evaluations [GRADE] assessment: moderate certainty) and OS of 0.7 (95% CI: 0.50–0.99; GRADE assessment: high certainty) in TNBC patients treated with AKT inhibitors. Regarding clinical benefit rate and overall response rate were 1.21 (95% CI 0.85–1.73; GRADE assessment: moderate certainty) and 1.26 (95% CI 0.91–1.73; GRADE assessment: low certainty). Only OS had a statistical difference. For the odd ratio of all grade AE and ≥3 grade AE in the therapeutic process was counted and pooled, 4.34 (95% CI 1.33–14.14; GRADE assessment: moderate certainty) and 1.76 (95% CI 1.28–2.41; GRADE assessment: moderate certainty), respectively. Conclusions: AKT inhibitors showed slightly better efficacy in the treatment of TNBC. However, further studies are needed to evaluate its long-term safety and optimal regimen, and caution should be exercised in patients with coexisting gastrointestinal disorders. The clinical characteristics of the patients and the choice of drugs should be considered on an individual basis.