Clinical efficacy and safety of anti-PD-1/PD-L1 inhibitors for the treatment of advanced or metastatic cancer: a systematic review and meta-analysis

Abstract

Anti-PD-1/PD-L1 inhibitors provide a survival advantage over conventional therapies for treatment of advanced or metastatic cancer. However, the factors determining which patients benefit the most from anti-PD-1/PD-L1 inhibitors are unknown, making treatment-related decisions difficult. We performed a systematic review and meta-analysis of acquired data to assess the efficacy and toxicity of anti-PD-1/ PD-L1 inhibitors in advanced and metastatic cancer. A thorough search strategy was applied to identify randomised controlled trials (RCTs) in Pubmed, Embase, Cochrane, and major conferences. Studies meeting predefined selection criteria were selected, and two independent investigators performed data extraction; overall survival (OS), progression-free survival (PFS), and overall response rate were compared between anti-PD-1/PD-L1 inhibitors and control therapies. We calculated the pooled response rate and 95% CIs of all-grade and high-grade (≥3) adverse effects and evaluated the withinstudy heterogeneity using subgroup, sensitivity, and meta-regression analyses. In final, we included eligible 35 RCTs (21047 patients). The main estimated hazard ratios (HRs) for OS and PFS were 0.76 (0.71-0.82) and 0.81 (0.73-0.89) in a random-effects model. The anti-PD-1/PD-L1 inhibitor group had a significantly high risk for all-grade immune-related adverse events. Anti-PD-1/PD-L1 inhibitors were identified as a preferable treatment option for advanced or metastatic cancer patients who are male, aged < 65 years, current or former smokers, had no CNS or liver metastasis, had not EGFR mutation, and had high PD-L1 expression.Cancer is a common cause of death, accounting for more than 9.56 million deaths annually 1 . Over half of cancer patients have a poor prognosis due to locally advanced or systemic metastasis. For the majority of these cases, treatment with conventional therapies, such as chemotherapy and radiotherapy, does not improve their prognosis. Recently, several immune checkpoint inhibitors (ICIs), have been developed and approved for a wide range of tumour types and having shown potential for maintaining homeostasis and eliminating tumour cells. Immunotherapies targeting immune checkpoint pathways have shown potential for generating a durable response and for prolonging disease stabilisation in a significant proportion of inoperable, advanced, or recurrent cancers in patients with multiple cancer types, along with favourable tolerability. In addition to their use as a monotherapy, the general safety of immune checkpoint agents also allows for their use in the development of combined therapies for cancer treatment; combining ICIs with other conventional treatments or targeted therapies is expected to improve anti-tumour activity and increase ICI efficacy. However, although durable responses were reported in cancer patients treated with combination strategies involving ICIs, it is still necessary to optimise dose selection to minimise the adverse events (AEs) caused by combination regimens while maintaining stable clinical ef...

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