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First-line immune-checkpoint inhibitor treatment in extensive-disease small-cell lung cancer: A classical and network meta-analysis

1 Department of Oncology, Istinye University School of Medicine, Istanbul, Turkey
2 Department of Oncology, Lara Medicalpark Hospital, Antalya, Turkey
3 Department of Oncology, Necmettin Erbakan University, Meram School of Medicine, Konya, Turkey
4 Department of Thoracic Surgery, Lara Medicalpark Hospital, Antalya, Turkey

Correspondence Address:
Hasan Mutlu,
Department of Oncology, Istinye University School of Medicine, Maltepe, Çırpıcı Yolu B Çk. No. 9, 34010 Zeytinburnu, İstanbul
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.jcrt_721_21

Background: Small-cell lung cancer (SCLC) has a poor prognosis. For the last 30 years, first-line systemic treatment has remained unaltered. After the integration of ımmunotherapy, a new first-line gold standard, atezolizumab in combination with carboplatin plus etoposide, was approved in extensive-disease SCLC (ED-SCLC) in 2019. Materials and Methods: First-line randomized controlled studies that investigated anti-programmed cell death protein 1 (PD-1)/PD-1 ligand-1 (PD-L1) and anti-T-lymphocyte-associated protein 4 (CTLA-4) agents in combination with platinum plus etoposide (EP) were scoured. A total of six studies (two – anti-CTLA-4 and four – anti-PD1/PD-L1) were included and classic and network meta-analyses (NMAs) were performed. Results: Fixed model for overall survival (OAS) in the PD-1- or PD-L1-treated subgroup yielded a hazard ratio (HR) of 0.746 with a 95% confidence interval (CI) =0.662–0.840 and in the CTLA-4-treated subgroup a HR of 0.941 with a 95% CI = 0.816–1.084 for the immune therapy + chemotherapy versus chemotherapy comparison (CTLA-4-based versus PD-1- or PD-L1-based groups' comparison of OAS effect Q = 6.05, df = 1, P = 0.014). NMA showed that all chemotherapy + immunotherapy combinations were equally potent and more efficient than PE in terms of OAS and progression-free survival (PFS). Rank probability plots demonstrated nivolumab + EP as the most probable effective treatment modality in terms of OAS and PFS. Conclusion: The usage of anti-PD1/PD-L1 immunotherapy agents results in significant OAS advantage, and anti-PD1/PD-L1 agents are superior to anti-CTLA-4 approach in combination with platinum plus etoposide regimen in ED-SCLC.

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