Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52-0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61-0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04-1.762, p = 0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug.

https://www.mdpi.com/2077-0383/10/7/1365/pdf

PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis.

Immune checkpoint inhibitors (ICI) as monotherapy in selected patients as well as in combination with chemotherapy have become the standard of care in the first-line treatment strategy of advanced non-small cell lung cancer (NSCLC) patients. Combination treatment with ICI, such as nivolumab and ipilimumab or durvaluamb and ipilimumab, has also been proposed as potential strategies in this setting in selected advanced NSCLC patients. Characterizing predictive markers of long-term clinical benefit with ICI is a critical objective. Tumor mutational burden has been proposed as a potential predictive biomarker. In this review, we discuss the efficacy of nivolumab and ipilimumab in advanced NSCLC patients as well as the clinical utility of tumor mutational burden in the efficacy of this combination. Ongoing clinical trials with nivolumab and ipilimumab, and the efficacy of this combination in subgroups of NSCLC patients, such as elderly patients and patients with brain metastases, are also discussed.

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Nivolumab plus ipilimumab combination therapy for the first-line treatment NSCLC: evidence to date.

CheckMate 592: A phase II exploratory study of biomarkers associated with the efficacy of first-line nivolumab (nivo) plus ipilimumab (ipi) in patients (pts) with stage IV or recurrent NSCLC

T. Beck

Papers

CheckMate 592: A phase II exploratory study of biomarkers associated with the efficacy of first-line nivolumab (nivo) plus ipilimumab (ipi) in patients (pts) with stage IV or recurrent NSCLC