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Review
. 2021 Mar 26;10(7):1365.
doi: 10.3390/jcm10071365.

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

Margarita Majem  1 , Manuel Cobo  2 , Dolores Isla  3 , Diego Marquez-Medina  4 , Delvys Rodriguez-Abreu  5 , Joaquín Casal-Rubio  6 , Teresa Moran Bueno  7 , Reyes Bernabé-Caro  8 , Diego Pérez Parente  9 , Pedro Ruiz-Gracia  9 , Marta Marina Arroyo  9 , Luis Paz-Ares  10
Affiliations
Review

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

Margarita Majem et al. J Clin Med. .

Abstract

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.

Keywords: PD-(L)1 inhibitors; efficacy; first-line treatment; immunotherapy; network meta-analysis; non-small cell lung cancer.

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Conflict of interest statement

M.M. reports advisory and consultancy honoraria from Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Amgen, Boehringer and Takeda; speaker honoraria from Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Bayer, Amgen and Boehringer; and travel/accommodation expenses from Roche, Merck and Lilly. M.C. reports advisory and consultancy honoraria from Roche, Bristol-Myers Squibb, AstraZeneca and Pfizer; and travel/accommodation expenses from Roche, Bristol-Myers Squibb and AstraZeneca. D.I. reports advisory and consultancy honoraria from Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Lilly, Pfizer, Bayer, Abbvie, Amgen and Boehringer and Takeda; speaker honoraria from Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Lilly, Pfizer, Bayer, Amgen, Boehringer and Sanofi; grant funding from Roche, Bristol-Myers Squibb, AstraZeneca and Lilly; and travel/accommodation expenses from Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Lilly, Pfizer, Amgen and Boehringer. D.M.-M. reports advisory and consultancy honoraria from Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Lilly, Pfizer and Boehringer; and speaker honoraria from Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Lilly, Pfizer and Boehringer. D.R.-A. reports advisory and consultancy honoraria from Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Pfizer, Boehringer and Takeda; speaker honoraria from Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Boehringer and Takeda; and travel/accommodation expenses from Roche, Merck, Bristol-Myers Squibb and AstraZeneca. J.C.-R. reports advisory and consultancy honoraria from Roche and AstraZeneca; and travel/accommodation expenses from Roche. T.M.-B. reports advisory and consultancy honoraria from Roche, Bristol-Myers Squibb, AstraZeneca and Boehringer; speaker honoraria from Merck, Bristol-Myers Squibb and AstraZeneca; and research grants from Kyowa Kirin. R.B.-C. reports advisory honoraria from Roche, Bristol-Myers Squibb and AstraZeneca; and speaker honoraria from Roche, Bristol-Myers Squibb and Amgen. L.P.-A. reports advisory honoraria from Roche, Merck (MSD), Merck Serono, Bristol-Myers Squibb, AstraZeneca, Lilly, Pfizer, PharmaMar, Bayer, Abbvie, Amgen, Janssen, GSK, Novartis, Ipsen, Boehringer, Takeda, Sanofi, Tesaro, Blueprint, Mirati; and research grants from Bristol-Myers Squibb, AstraZeneca and PharmaMar. Additionally, he is a co-founder and board member of Altum Sequencing, as well as an external board member of Genomica. D.P.-P., P.R.-G. and M.M.A. were full-time employees of Roche Farma S.A. at the time the study was conducted.

Figures

Figure 1
Figure 1
Flow chart of study selection (up to 1 November 2020). RCTs, randomized controlled trials * Other studies included pooled analyses, post-marketing studies, clinical trial protocols, patient-reported outcome assessments and any study on biomarkers/gene profiling. ** Two publications (one of them presented at the ASCO congress) were included for one of the trials (KEYNOTE-024 [10,33]).
Figure 2
Figure 2
Forest plot of pooled hazard ratios for (A) progression-free survival (PFS) and (B) overall survival (OS) in patients who received PD-1/PD-L1 inhibitors vs. chemotherapy alone. HR, hazard ratio; CI, confidence interval.
Figure 3
Figure 3
Forest plot of hazard ratios for overall survival (OS) in the subgroup analysis. HR, hazard ratio; CI, confidence interval. * Only KEYNOTE-042 included patients with stage III NSCLC.
See this image and copyright information in PMC

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