Efficacy of PI3K/AKT/mTOR pathway inhibitors for the treatment of advanced solid cancers: A literature-based meta-analysis of 46 randomised control trials.

Abstract

The phosphatidylinositol-3- kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway (PI3K/AKT/mTOR pathway) plays a key role in cancer. We performed this meta-analysis to assess the clinical effect of using PI3K/AKT/mTOR pathway inhibitors on advanced solid tumours. All the randomised controlled trials (RCT) that compared the therapy with PI3K/AKT/mTOR pathway inhibitors with other therapies were included. The main end-point was progression-free survival (PFS); other end-points included overall survival (OS) and objective response rate (ORR). A subgroup analysis was performed mainly for PFS. In total, 46 eligible RCT were included. The pooled results showed that PI3K/AKT/mTOR pathway inhibitor-based regimens significantly improved the PFS of patients with advanced solid tumours (hazard ratios (HR) = 0.79; 95% confidence intervals (CI): 0.71-0.88) and PI3K pathway mutations (HR = 0.69; 95% CI: 0.56-0.85). All single PI3K/AKT/mTOR pathway inhibitor therapies were compared with other targeted therapies (HR = 0.99; 95% CI: 0.93-1.06) and dual targeted therapies, including PI3K/AKT/mTOR pathway inhibitors and other targeted therapies (HR = 1.04; 95% CI: 0.62-1.74), which showed no significant differences in the PFS. Additional PI3K/AKT/mTOR pathway inhibitors showed no advantage with respect to the OS (HR = 0.98; 95% CI: 0.90-1.07) or ORR (risk ratio (RR) = 1.02; 95% CI: 0.87-1.20). Our meta-analysis results suggest that the addition of the PI3K pathway inhibitors to the therapy regiment for advanced solid tumours significantly improves PFS. The way that patients are selected to receive the PI3K pathway inhibitors might be more meaningful in the future.