The efficacy and safety of PD-1/PD-L1 inhibitors in breast cancer: a systematic review and meta-analysis

Background: Immune checkpoint inhibition has been increasingly used in breast cancer therapy. Understanding the benefit and risk of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors is critical for clinical practice. This study aims to determine the objective response, disease control and adverse events of breast cancer patients treated with PD-1/PD-L1 inhibitors. Methods: PubMed, Cochrane Library, Web of Science and EMBASE databases were searched up to Aug 1, 2019. Both nonrandomized and randomized studies were included. Pooled objective response rate (ORR), disease control rate (DCR) and adverse events were pooled analyzed. Results: A total of nine clinical studies were identified. Triple-negative breast cancer (TNBC) showed the highest estimates of ORR [overall population: 49.7%, 95% confidence interval (CI): 33.9-65.5%; PD-L1 positive population: 55.8%, 95% CI: 42.9-68.8%] and DCR (overall population: 67.5%, 95% CI: 38.6-96.4%; PD-L1 positive population: 83.4%, 95% CI: 72.2-94.5%) post-anti-PD-L1 plus nab-paclitaxel treatment. With respect to grade >= 3 treatment related adverse events, the pooled estimates ranged from 12.0% to 50.9% for anti-PD-1/PD-L1 monotherapy. The pooled estimates percentages of grade >= 3 treatment related adverse events in TNBC patients treated with anti-PD-L1 plus nab-paclitaxel were 59.6% (95% CI: 36.1-83.0). Conclusions: We presented the aggregate estimates of ORR, DCR, and treatment related adverse events for breast cancer patients receiving anti-PD-1/PD-L1 treatment. However, these results were largely derived from single-arm studies, and randomized studies with head-to-head comparison of PD-1/PD-L1 inhibitors and chemotherapy are lacking. Additionally, the incidence of varying treatment related adverse events should be also carefully monitored.