BACKGROUND/AIM: Cemiplimab in patients with non-small cell lung cancer (NSCLC) with PD-L1 (programmed death ligand type 1) expression ≥50% showed a significant improved overall survival (OS) with increasing expression of PD-L1. To our knowledge there exist no similar data published for pembrolizumab regarding the increased OS in relation to the PD-L1 expression. Therefore, the objective of our study was to determine whether improvement in OS reflects increased expression levels of PD-L1 (≥50%) in patients with NSCLC. PATIENTS AND METHODS: Retrospective data from 9 Czech and 1 Polish comprehensive oncology Centers were used. All patients with stage IV NSCLC and PD-L1 expression ≥50% treated with pembrolizumab in daily practice were included. The groups of patients according to the expression of PD-L1 were determined as follows: PD-L1 50-59%, 60-69%, 70-79%, 80-89% and 90-100%. The log-rank test and the Cox regression model were used to compare survival between study groups. RESULTS: A total of 617 patients were included in the study. We did not observe a statistically significant difference in OS between groups of patients with different levels of PD-L1 expression in the pooled comparison (p=0.445). Furthermore, we did not observe a statistically significant difference even when comparing OS in patients with PD-L1expression of 50-59% (reference) with the group of other patients according to the level of expression of PD-L1 in the Cox regression model including the effect covariates. CONCLUSION: PD-L1 expression showed no significant effect on OS in patients with NSCLC with PD-L1≥50% treated with pembrolizumab.

Department of Lung Cancer and Chest Tumours Maria Sklodowska Curie National Research Institute of Cancer Warsaw Poland

Department of Oncology Liberec Regional Hospital Liberec Czech Republic

Department of Pneumology and Phthiseology University Hospital and Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic;

Department of Pneumology Bulovka Hospital 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Pulmonology Motol University Hospital 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Respiratory Diseases Faculty of Medicine and University Hospital Brno Masaryk University Brno Czech Republic

Department of Respiratory Medicine Thomayer Hospital 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Respiratory Medicine University Hospital Olomouc Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic

Department of Social and Clinical Pharmacy Faculty of Pharmacy in Hradec Kralove Charles University Hradec Kralove Czech Republic

Multiscan Pardubice Oncology Centre Pardubice Hospital Pardubice Czech Republic

OAKS Consulting s r o Prague Czech Republic

Pulmonary Department University Hospital Hradec Kralove Faculty of Medicine in Hradec Kralove Charles University Hradec Kralove Czech Republic

Zobrazit více v PubMed

Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O’Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR, KEYNOTE-024 Investigators Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–1833. doi: 10.1056/NEJMoa1606774. PubMed DOI

Özgüroğlu M, Kilickap S, Sezer A, Gümüş M, Bondarenko I, Gogishvili M, Nechaeva M, Schenker M, Cicin I, Ho GF, Kulyaba Y, Zyuhal K, Scheusan RI, Garassino MC, He X, Kaul M, Okoye E, Li Y, Li S, Pouliot JF, Seebach F, Lowy I, Gullo G, Rietschel P. First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with pd-l1 50% or more (empower-lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(9):989–1001. doi: 10.1016/S1470-2045(23)00329-7. PubMed DOI

Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, Özgüroğlu M, Zou W, Sandler A, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, McCleland M, Mocci S, Jassem J, Spigel DR. Atezolizumab for first-line treatment of PD-L1–selected patients with NSCLC. N Engl J Med. 2020;383(14):1328–1339. doi: 10.1056/NEJMoa1917346. PubMed DOI

Di Federico A, De Giglio A, Parisi C, Gelsomino F, Ardizzoni A. PD-1/PD-L1 inhibitor monotherapy or in combination with chemotherapy as upfront treatment for advanced NSCLC with PD-L1 expression ≥ 50%: Selecting the best strategy. Crit Rev Oncol Hematol. 2021;160:103302. doi: 10.1016/j.critrevonc.2021.103302. PubMed DOI

Zhou Y, Lin Z, Zhang X, Chen C, Zhao H, Hong S, Zhang L. First-line treatment for patients with advanced non-small cell lung carcinoma and high PD-L1 expression: pembrolizumab or pembrolizumab plus chemotherapy. J Immunother Cancer. 2019;7(1):120. doi: 10.1186/s40425-019-0600-6. PubMed DOI PMC

Aguiar PN Jr, De Mello RA, Hall P, Tadokoro H, Lima Lopes G. PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data. Immunotherapy. 2017;9(6):499–506. doi: 10.2217/imt-2016-0150. PubMed DOI

Aguiar PN Jr, Santoro IL, Tadokoro H, de Lima Lopes G, Filardi BA, Oliveira P, Mountzios G, de Mello RA. The role of PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: a network meta-analysis. Immunotherapy. 2016;8(4):479–488. doi: 10.2217/imt-2015-0002. PubMed DOI

Alessi JV, Elkrief A, Ricciuti B, Wang X, Cortellini A, Vaz VR, Lamberti G, Frias RL, Venkatraman D, Fulgenzi CAM, Pecci F, Recondo G, Di Federico A, Barrichello A, Park H, Nishino M, Hambelton GM, Egger JV, Ladanyi M, Digumarthy S, Johnson BE, Christiani DC, Lin X, Gainor JF, Lin JJ, Pinato DJ, Schoenfeld AJ, Awad MM. Clinicopathologic and genomic factors impacting efficacy of first-line chemoimmunotherapy in advanced NSCLC. J Thorac Oncol. 2023;18(6):731–743. doi: 10.1016/j.jtho.2023.01.091. PubMed DOI PMC

Sezer A, Kilickap S, Gümüş M, Bondarenko I, Özgüroğlu M, Gogishvili M, Turk HM, Cicin I, Bentsion D, Gladkov O, Clingan P, Sriuranpong V, Rizvi N, Gao B, Li S, Lee S, McGuire K, Chen CI, Makharadze T, Paydas S, Nechaeva M, Seebach F, Weinreich DM, Yancopoulos GD, Gullo G, Lowy I, Rietschel P. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021;397(10274):592–604. doi: 10.1016/S0140-6736(21)00228-2. PubMed DOI

Hendriks LE, Kerr KM, Menis J, Mok TS, Nestle U, Passaro A, Peters S, Planchard D, Smit EF, Solomon BJ, Veronesi G, Reck M, ESMO Guidelines Committee Non-oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(4):358–376. doi: 10.1016/j.annonc.2022.12.013. PubMed DOI

Edahiro R, Kanazu M, Kurebe H, Mori M, Fujimoto D, Taniguchi Y, Suzuki H, Hirano K, Yokoyama T, Morita M, Fukuda Y, Uchida J, Makio T, Tamiya M. Clinical outcomes in non-small cell lung cancer patients with an ultra-high expression of programmed death ligand-1 treated using pembrolizumab as a first-line therapy: A retrospective multicenter cohort study in Japan. PLoS One. 2019;14(7):e0220570. doi: 10.1371/journal.pone.0220570. PubMed DOI PMC

Park S, Choi YD, Kim J, Kho BG, Park CK, Oh IJ, Kim YC. Efficacy of immune checkpoint inhibitors according to PD-L1 tumor proportion scores in non-small cell lung cancer. Thorac Cancer. 2020;11(2):408–414. doi: 10.1111/1759-7714.13284. PubMed DOI PMC

Shah M, Hubbard RA, Mamtani R, Marmarelis ME, Hennessy S. Very high PD-L1 expression as a prognostic indicator of overall survival among patients with advanced non-small cell lung cancer receiving anti-PD-(L)1 monotherapies in routine practice. Pharmacoepidemiol Drug Saf. 2022;31(10):1121–1126. doi: 10.1002/pds.5487. PubMed DOI PMC

Shah M, Mamtani R, Marmarelis ME, Hennessy S. Chemoimmunotherapy vs. immunotherapy for first line treatment of advanced non-small cell lung cancer with a PD-L1 expression ≥50% or ≥90. Clin Lung Cancer. 2023;24(3):235–243. doi: 10.1016/j.cllc.2023.02.007. PubMed DOI PMC

Brody R, Zhang Y, Ballas M, Siddiqui MK, Gupta P, Barker C, Midha A, Walker J. PD-L1 expression in advanced NSCLC: Insights into risk stratification and treatment selection from a systematic literature review. Lung Cancer. 2017;112:200–215. doi: 10.1016/j.lungcan.2017.08.005. PubMed DOI

Bassanelli M, Sioletic S, Martini M, Giacinti S, Viterbo A, Staddon A, Liberati F, Ceribelli A. Heterogeneity of PD-L1 expression and relationship with biology of NSCLC. Anticancer Res. 2018;38(7):3789–3796. doi: 10.21873/anticanres.12662. PubMed DOI

An HJ, Yang JW, Kim MH, Song DH. PD-L1 and PD-1 expression in early stage uterine endometrioid carcinoma. In Vivo. 2024;38(1):246–252. doi: 10.21873/invivo.13431. PubMed DOI PMC

Cavaille F, Peretti M, Garcia ME, Giorgi R, Ausias N, Vanelle P, Barlesi F, Montana M. Real-world efficacy and safety of pembrolizumab in patients with non-small cell lung cancer: a retrospective observational study. Tumori. 2021;107(1):32–38. doi: 10.1177/0300891620926244. PubMed DOI

Tamiya M, Tamiya A, Hosoya K, Taniguchi Y, Yokoyama T, Fukuda Y, Hirano K, Matsumoto H, Kominami R, Suzuki H, Hirashima T, Uchida J, Morita M, Kanazu M, Sawa N, Kinoshita Y, Hara S, Kumagai T, Fujimoto D. Efficacy and safety of pembrolizumab as first-line therapy in advanced non-small cell lung cancer with at least 50% PD-L1 positivity: a multicenter retrospective cohort study (HOPE-001) Invest New Drugs. 2019;37(6):1266–1273. doi: 10.1007/s10637-019-00843-y. PubMed DOI

Geiger-Gritsch S, Olschewski H, Kocher F, Wurm R, Absenger G, Flicker M, Hermann A, Heininger P, Fiegl M, Zechmeister M, Endel F, Wild C, Pall G. Real-world experience with anti-PD-1/PD-L1 monotherapy in patients with non-small cell lung cancer. Wien Klin Wochenschr. 2021;133(21-22):1122–1130. doi: 10.1007/s00508-021-01940-w. PubMed DOI

Ricciuti B, Elkrief A, Alessi JVM, Wang X, Barrichello APDC, Pecci F, Lamberti G, Lindsay J, Sharma B, Felt K, Nishino M, Sholl LM, Rodig SJ, Schoenfeld AJ, Awad MM. Three-year outcomes and correlative analyses in patients with non–small cell lung cancer (NSCLC) and a very high PD-L1 tumor proportion score (TPS) ≥ 90% treated with first-line pembrolizumab. J Clin Oncol. 2022;40(16_suppl):9043–9043. doi: 10.1200/JCO.2022.40.16_suppl.9043. DOI

Velcheti V, Hu X, Yang L, Pietanza MC, Burke T. Long-term real-world outcomes of first-line pembrolizumab monotherapy for metastatic non-small cell lung cancer with ≥50% expression of programmed cell death-ligand 1. Front Oncol. 2022;12:834761. doi: 10.3389/fonc.2022.834761. PubMed DOI PMC

Cortellini A, Cannita K, Tiseo M, Cortinovis DL, Aerts JGJV, Baldessari C, Giusti R, Ferrara MG, D’Argento E, Grossi F, Guida A, Berardi R, Morabito A, Genova C, Antonuzzo L, Mazzoni F, De Toma A, Signorelli D, Gelibter A, Targato G, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Mansueto G, Zoratto F, Filetti M, Bracarda S, Citarella F, Russano M, Cantini L, Nigro O, Buti S, Minuti G, Landi L, Ricciardi S, Migliorino MR, Natalizio S, Simona C, De Filippis M, Metro G, Adamo V, Russo A, Spinelli GP, Di Maio M, Banna GL, Friedlaender A, Addeo A, Pinato DJ, Ficorella C, Porzio G. Post-progression outcomes of NSCLC patients with PD-L1 expression ≥ 50% receiving first-line single-agent pembrolizumab in a large multicentrereal-world study. Eur J Cancer. 2021;148:24–35. doi: 10.1016/j.ejca.2021.02.005. PubMed DOI