PD-1/L1 With or Without CTLA-4 Inhibitors Versus Chemotherapy in Advanced Non-Small Cell Lung Cancer

Abstract

Background With the use of immune-checkpoint inhibitors (ICIs) in advanced or metastatic non-small cell lung cancer (NSCLC), whether ICIs or chemotherapy is more effective still remains controversial. This study was conducted to evaluate the efficacy of programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), cytotoxic T-lymphocyte protein 4 (CTLA-4) alone or in their combination vs chemotherapy in patients with advanced or metastatic NSCLC. Methods This meta-analysis was conducted from PubMed, Web of Science, Medline, Embase, and the Cochrane Library up to March 2021 to identify relevant randomized controlled trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint was adverse events (AEs). This meta-analysis’s Prospero registration number is CRD42022323570. Results The search process has identified 13 studies containing 7918 patients with advanced or metastatic NSCLC. The benefit of PD-1/L1 or CTLA-4 inhibitors alone or in combination compared with chemotherapy for advanced or metastatic NSCLC was elucidated in both OS [HR = .75, 95% CI (.70-.80), P < .001] and PFS [HR = .83, 95% CI (.73-.95), P < .001]. Besides, ICIs were associated with fewer AEs compared to chemotherapy. Conclusion PD-1/L1 or CTLA-4 inhibitors alone or in combination, with fewer AEs, was associated with significant improvements in terms of OS and PFS than chemotherapy in advanced or metastatic NSCLC.

Identification of RFC4 as a potential biomarker for pan‐cancer involving prognosis, tumour immune microenvironment and drugs

“…Several studies have reported a correlation between higher TMB and ICI efficacy, indicating that TMB could serve as a reliable predictive biomarker. 38 , 40 , 41 , 42 This study examines the correlation between RFC4 expression and TMB and MSI levels based on TCGA data. The results indicate that RFC4 expression is correlated with TMB and MSI levels in BLCA, COAD, KICH, KIRC, LGG, LUAD, PRAD, READ, SKCM, STAD and UCEC.…”

“…Therefore, TMB can serve as a reliable indicator of the effectiveness of ICI, and tumours with higher TMB are more likely to respond favourably to cancer immunotherapy. Several studies have reported a correlation between higher TMB and ICI efficacy, indicating that TMB could serve as a reliable predictive biomarker 38,40–42 . This study examines the correlation between RFC4 expression and TMB and MSI levels based on TCGA data.…”

Combining PD-1 or PD-L1 inhibitors with chemotherapy is a good strategy for the treatment of extensive small cell lung cancer: A retrospective analysis of clinical studies

“…ICIs can block the negative costimulatory signalling pathway of T cells, thereby improving the body’s antitumour immune response and promoting the clearance of T cells to tumour cells ( 11 , 12 ). At present, ICIs that are mainly used in clinical practice include cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors, programmed cell death 1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors ( 13 ). ICIs targeting CTLA-4 and PD-1/PD-L1 can block the immune checkpoint pathway to restore the body’s antitumour immune response and exert antitumour effects.…”