Pembrolizumab in PD-L1-positive advanced non-small cell lung carcinoma: A meta-analysis of survival benefits and immune-related toxicity events patterns: Original scientific article

Alendra Chakramurty; Adetya  Rahma Dinni; Ihda  Silvia; Aprilyan  Laras Cantika; Citrawati  Dyah Kencono Wungu

doi:10.5599/admet.2956

Authors

Alendra Chakramurty Department of Anatomical Pathology, Faculty of Medicine, Universitas Swadaya Gunung Jati, Cirebon, Indonesia https://orcid.org/0009-0001-0304-8195
Adetya Rahma Dinni Department of Pulmonology, Faculty of Medicine, Universitas Swadaya Gunung Jati, Cirebon, Indonesia https://orcid.org/0000-0002-6238-3196
Ihda Silvia Department of Internal Medicine, Gunung Jati General Hospital, Cirebon, Indonesia https://orcid.org/0009-0004-1977-8960
Aprilyan Laras Cantika Department of Medical Education and Bioethics, Faculty of Medicine, Universitas Swadaya Gunung Jati, Cirebon, Indonesia https://orcid.org/0000-0001-5491-9109
Citrawati Dyah Kencono Wungu Department of Physiology and Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia https://orcid.org/0009-0003-4972-2100

DOI:

https://doi.org/10.5599/admet.2956

Keywords:

pembrolizumab, meta-analysis, non-small cell lung cancer, PD-L1, immunotherapy, biomarker

Abstract

Background and objective: Pembrolizumab has shown significant therapeutic benefit in advanced non-small cell lung cancer (NSCLC), but it remains uncertain which patients will benefit the most, and recent data suggest that programmed death-ligand 1 (PD-L1) expression as a single predictive biomarker is insufficient. This systematic review and meta-analysis looked at the safety and efficacy of pembrolizumab in PD-L1-positive advanced NSCLC patients, with a particular focus on disparities in treatment response to PD-L1 level of expression and demographic characteristics. Method: According to the PRISMA 2020 guidelines, six large databases were searched up to March 2025 for randomized controlled trials comparing pembrolizumab with chemotherapy in patients with such conditions. Overall survival (OS) and progression-free survival (PFS) were chosen as primary outcomes, and overall response rate (ORR) and safety profiles as secondary endpoints. A meta-analysis was conducted using a random-effects model, and the Cochrane risk of bias (ROB2) tool was employed to evaluate study quality. Seven randomized controlled trials involving 4,900 patients were included in the analysis. Key results: Pembrolizumab had a substantially better performance compared to chemotherapy for all the measures of efficacy: OS (hazard ratio (HR) 0.65, 95 % confidence interval (CI): 0.57 to 0.73, P < 0.00001), PFS (HR 0.55, 95 % CI: 0.42 to 0.72, P < 0.0001) and ORR (relative risk 2.10, 95 % CI: 1.51 to 2.93, P < 0.0001). Subgroup analysis showed greater survival benefit in patients younger than 65 years (OS HR 0.55) compared to patients aged 65 and older (OS HR 0.72), and in females (OS HR 0.44) compared to males (OS HR 0.67). Of most significant importance, those with PD-L1 expression <1 % also saw considerable benefit in survival (OS HR 0.60), casting doubts over the existing biomarker-based selection criteria. Conclusion: In conclusion, pembrolizumab achieves clinically meaningful survival benefits and an acceptable toxicity in PD-L1-positive advanced NSCLC. The high efficacy observed even in low PD-L1 expressers, and demographic differences in drug response, suggest that existing patient selection criteria could potentially be extended. These findings justify the application of a more advanced approach involving multiple biomarkers for more precise treatment allocation.

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