Efficacy of PD-1/PD-L1 inhibitors against pretreated advanced cancer: a systematic review and meta-analysis

BACKGROUND: Programmed cell death 1 (PD-1) and programmed cell death-ligand 1(PD-L1) inhibitors have captured our attention as new therapeutic options for several tumor types. Nonetheless, the differences in efficacy between PD-1/PD-L1 inhibitors and conventional treatments (chemotherapy or targeted therapy) in pretreated advanced cancer patients remain unclear. MATERIALS AND METHODS: A systematic literature search was conducted to identify phase III randomized controlled trials (RCTs)-based investigations of PD-1(nivolumab, pembrolizumab)/PD-L1 inhibitors (atezolizumab) against pretreated advanced cancer. We evaluated these trials for inclusion, assessed each study’s risk of bias and selected relevant data for analysis. RESULTS: The eligibility criteria were met by 5,093 patients from 8 phase III RCTs. PD-1/PD-L1 inhibitors significantly extended overall survival relative to the conventional treatment, expressed as hazard ratio [HR] (0.72, 95% CI, 0.66 to 0.77, P < 0.001) and median month difference (2.83 months, 95% CI, 1.87 to 3.78, P < 0.001). The progression-free survival HRs favored PD-1/PD-L1 inhibitors over conventional treatment (0.88; 95% CI, 0.82 to 0.95, P = 0.002), whereas median month difference was just the opposite (−0.69 months, 95% CI, −1.14 to −0.24, P < 0.001). CONCLUSIONS: Among selected patients with pretreated advanced cancer, PD-1/PD-L1 inhibitors, compared with conventional treatments (chemotherapy or targeted therapy), were associated with improvement in overall survival (2.83 months) but not progression-free survival. These findings will be important in considering PD-1/PD-L1 inhibitors in the treatment of pretreated advanced cancer and have implications for future study design.