Indian J Cancer. 2026 Jan 1;63(1):9-17. doi: 10.4103/ijc.ijc_225_24. Epub 2026 Jun 9.
ABSTRACT
BACKGROUND: To assess the efficacy and safety of first-line programmed-death 1 (PD-1)/programmed-death ligand 1 (PD-L1) inhibitors + chemotherapy for driver-gene negative advanced non-squamous non-small cell lung cancer (NSCLC).
METHODS: Eligible literature was identified following a systematic search of four electronic databases (PubMed, Embase, Ovid, and Cochrane library databases) from their inception to June, 2023. Unpublished research was searched from the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and the World Conference on Lung Cancer (WCLC) meeting abstracts. Review Manager 5.3 software was used for analysis.
RESULTS: Nine randomized controlled trials (RCTs) were identified and included, involving 3443 driver-gene negative advanced non-squamous NSCLC patients. PD-1/PD-L1 inhibitors + chemotherapy had significantly longer progression-free survival (PFS) (hazard ratio [HR] = 0.57, 95% CI = 0.52-0.61, P < 0.00001), and overall survival (OS) (HR = 0.69, 95% confidence interval = 0.63-0.76, P < 0.00001) compared with chemotherapy alone. Analysis was performed based on PD-L1 expression levels; patients with any PD-L1 expression had PFS benefit ( P < 0.00001), while only patients with PD-L1 ≥50% ( P = 0.02) and PD-L1 ≤1% ( P = 0.0009) had OS benefit. Regarding liver metastases, there was no statistically significant benefit of PD-1/PD-L1 inhibitors + chemotherapy regimens for the liver metastases cohort in OS ( P = 0.08). In brain metastasis patients, PD-1/PD-L1 inhibitors + chemotherapy regimens demonstrated an improvement in PFS compared to chemotherapy ( P = 0.03).
CONCLUSION: Our results show that PD-1/PD-L1 inhibitors + chemotherapy showed better survival benefits than chemotherapy in driver-gene negative advanced non-squamous NSCLC patients.
PMID:42301654 | DOI:10.4103/ijc.ijc_225_24
