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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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References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Planchard D., Popat S., Kerr K., Novello S., Smit E.F., Faivre-Finn C., Mok T.S., Reck M., Van Schil P.E., Hellmann M.D., et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2018;29:iv192–iv237. doi: 10.1093/annonc/mdy275. - DOI - PubMed
    1. Goldstraw P., Chansky K., Crowley J., Rami-Porta R., Asamura H., Eberhardt W.E., Nicholson A.G., Groome P., Mitchell A., Bolejack V. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J. Thorac. Oncol. 2016;11:39–51. doi: 10.1016/j.jtho.2015.09.009. - DOI - PubMed
    1. Paz-Ares L.G., de Marinis F., Dediu M., Thomas M., Pujol J.L., Bidoli P., Molinier O., Sahoo T.P., Laack E., Reck M., et al. PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J. Clin. Oncol. 2013;31:2895–2902. doi: 10.1200/JCO.2012.47.1102. - DOI - PubMed
    1. Liang J., Ming L., Qihai S., Zhengyang H., Yunyi B., Yiwei H., Cheng Z., Wei J., Qun W., Lijie T. Compare the efficacy and safety of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors for advanced non-small cell lung cancer: A Bayesian analysis. Transl. Lung Cancer Res. 2020;9:1302–1323. doi: 10.21037/tlcr-20-192. - DOI - PMC - PubMed

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