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).