Comparative efficacy and safety of PD‐1 versus PD‐L1 inhibitors in breast cancer treatment: A systematic review and meta analysis

The comparative efficacy and safety of programmed death-ligand 1 (PD-L1) inhibitors versus programmed death protein 1 (PD-1) inhibitors in breast cancer treatment remain inconclusive, as no head-to-head randomized controlled trials (RCTs) conducted. This study aims to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors as monotherapy or in combination with chemotherapy for breast cancer. A systematic review and meta-analysis were performed using major databases and oncology conference proceedings. The primary outcomes were overall survival (OS) for advanced breast cancer and pathological complete response (PCR) rate for early breast cancer. Secondary outcomes included progression-free survival (PFS) for advanced breast cancer and incidence of adverse events (AEs). Seventeen studies met the inclusion criteria, consisting of seven RCTs on early-stage and 10 on advanced breast cancer. For advanced breast cancer, PD-1/PD-L1 inhibitors modestly improved OS compared to chemotherapy, with no significant differences between PD-1 and PD-L1 inhibitors. PD-L1 inhibitors showed greater improvement in PFS compared to PD-1 inhibitors. The likelihood of AEs of any grade was higher with PD-L1 inhibitor treatment than with PD-1 inhibitor treatment. In early breast cancer, combining PD-1/PD-L1 inhibitors with chemotherapy inducing higher PCR rates than chemotherapy alone, with PD-1 inhibitors achieving better outcomes than PD-L1 inhibitors. PD-1 inhibitors were linked to slightly higher rates of grade >2 AEs compared to PD-L1 inhibitors. The findings indicate that PD-1 inhibitors may offer advantages for advanced breast cancer due to similar OS and a lower rate of AEs. For early breast cancer, PD-1 inhibitors are recommended given their superior PCR rates.