Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Pembrolizumab for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer: Analysis of Prognostic Factors of Outcomes

Author(s): Carmelo Tibaldi*, Francesca Mazzoni, Vieri Scotti, Enrico Vasile, Daniele Pozzessere, Irene Stasi, Andrea Camerini, Francesca Federici, Giulia Meoni, Chiara Caparello, Marianna Turrini, Virginia Rossi , Lucia Pia Ciccone, Irene Pecora, Beatrice Fantechi, Lorenzo Antonuzzo, Diana Giannarelli and Editta Baldini

Volume 22, Issue 7, 2022

Published on: 27 July, 2021

Page: [1278 - 1285] Pages: 8

DOI: 10.2174/1871520621666210727112212

Price: $65

Abstract

Background: In advanced non-small-cell lung cancer, without activating mutations and with PD-L1≥50%, Pembrolizumab monotherapy is the therapeutic standard in Europe.

Objective: To evaluate retrospectively the safety and efficacy of this drug and to investigate potential prognostic factors in daily clinical practice.

Methods: From September 2017 to September 2019, 205 consecutive patients from 14 Italian Medical Oncology Units were enrolled in the study. Gender, Age (> or <70 years), ECOG-PS (0-1 or 2), histology (squamous or nonsquamous), presence of brain, bone and liver metastases at baseline, PD-L1 score (>90% or <90%), smoking status (never or former or current) were applied to the stratified log-rank. Cox’s proportional hazards model was used for multivariate analysis.

Results: At a median follow-up of 15.2 months, median progression-free and overall survival (mPFS and mOS) were 9.2 months (95% C.I., 4.8-13.5) and 15.9 months (95% C.I., not yet evaluable), respectively. Patients with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 had mPFS of 2.8 months (95% C.I., 2.1-3.4) and mOS of 3.9 months (95% C.I., 2.5-5.3). Patients with liver metastases at diagnosis had an mPFS of 3.2 months (95% C.I., 0.6-5.8) and an mOS of 6.0 months (95% C.I., 3.7-8.4). At multivariate analysis for OS gender, ECOG-PS 2, and presence of liver metastases were independent prognostic factors.

Conclusion: Patients with ECOG-PS 2 derived little benefit from the use of first-line pembrolizumab. In patients with liver metastases, the association of pembrolizumab with platinum-based chemotherapy could be a better option than pembrolizumab alone.

Keywords: NSCLC, pembrolizumab, liver metastases, prognostic factors, platinum-based chemotherapy, PD-L1.

Graphical Abstract
[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin., 2020, 70(1), 7-30.
[http://dx.doi.org/10.3322/caac.21590] [PMID: 31912902]
[2]
Garon, E.B.; Rizvi, N.A.; Hui, R.; Leighl, N.; Balmanoukian, A.S.; Eder, J.P.; Patnaik, A.; Aggarwal, C.; Gubens, M.; Horn, L.; Carcereny, E.; Ahn, M.J.; Felip, E.; Lee, J.S.; Hellmann, M.D.; Hamid, O.; Goldman, J.W.; Soria, J.C.; Dolled-Filhart, M.; Rutledge, R.Z.; Zhang, J.; Lunceford, J.K.; Rangwala, R.; Lubiniecki, G.M.; Roach, C.; Emancipator, K.; Gandhi, L. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med., 2015, 372(21), 2018-2028.
[http://dx.doi.org/10.1056/NEJMoa1501824] [PMID: 25891174]
[3]
Herbst, R.S.; Baas, P.; Kim, D-W.; Felip, E.; Pérez-Gracia, J.L.; Han, J-Y.; Molina, J.; Kim, J-H.; Arvis, C.D.; Ahn, M-J.; Majem, M.; Fidler, M.J.; de Castro, G., Jr; Garrido, M.; Lubiniecki, G.M.; Shentu, Y. Im, E.; Dolled-Filhart, M.; Garon, E.B. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet, 2016, 387(10027), 1540-1550.
[http://dx.doi.org/10.1016/S0140-6736(15)01281-7] [PMID: 26712084]
[4]
Reck, M.; Rodríguez-Abreu, D.; Robinson, A.G.; Hui, R.; Csőszi, T.; Fülöp, A.; Gottfried, M.; Peled, N.; Tafreshi, A.; Cuffe, S.; O’Brien, M.; Rao, S.; Hotta, K.; Leiby, M.A.; Lubiniecki, G.M.; Shentu, Y.; Rangwala, R.; Brahmer, J.R. Pembrolizumab versus chemotherapy for pd-l1-positive non-small-cell lung cancer. N. Engl. J. Med., 2016, 375(19), 1823-1833.
[http://dx.doi.org/10.1056/NEJMoa1606774] [PMID: 27718847]
[5]
Mok, T.S.K.; Wu, Y.L.; Kudaba, I.; Kowalski, D.M.; Cho, B.C.; Turna, H.Z.; Castro, G., Jr; Srimuninnimit, V.; Laktionov, K.K.; Bondarenko, I.; Kubota, K.; Lubiniecki, G.M.; Zhang, J.; Kush, D.; Lopes, G. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): A randomised, open-label, controlled, phase 3 trial. Lancet, 2019, 393(10183), 1819-1830.
[http://dx.doi.org/10.1016/S0140-6736(18)32409-7] [PMID: 30955977]
[6]
Reck, M.; Rodríguez-Abreu, D.; Robinson, A.G.; Hui, R.; Csőszi, T.; Fülöp, A.; Gottfried, M.; Peled, N.; Tafreshi, A.; Cuffe, S.; O’Brien, M.; Rao, S.; Hotta, K.; Vandormael, K.; Riccio, A.; Yang, J.; Pietanza, M.C.; Brahmer, J.R. Updated analysis of KEYNOTE-024: Pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J. Clin. Oncol., 2019, 37(7), 537-546.
[http://dx.doi.org/10.1200/JCO.18.00149] [PMID: 30620668]
[7]
Rimm, D.L.; Han, G.; Taube, J.M.; Yi, E.S.; Bridge, J.A.; Flieder, D.B.; Homer, R.; West, W.W.; Wu, H.; Roden, A.C.; Fujimoto, J.; Yu, H.; Anders, R.; Kowalewski, A.; Rivard, C.; Rehman, J.; Batenchuk, C.; Burns, V.; Hirsch, F.R.; Wistuba, I.I. A prospective multi-institutional, pathologist based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small-cell lung cancer. JAMA Oncol., 2017, 3(8), 1051-1058.
[http://dx.doi.org/10.1001/jamaoncol.2017.0013] [PMID: 28278348]
[8]
Hirsch, F.R.; McElhinny, A.; Stanforth, D.; Ranger-Moore, J.; Jansson, M.; Kulangara, K.; Richardson, W.; Towne, P.; Hanks, D.; Vennapusa, B.; Mistry, A.; Kalamegham, R.; Averbuch, S.; Novotny, J.; Rubin, E.; Emancipator, K.; McCaffery, I.; Williams, J.A.; Walker, J.; Longshore, J.; Tsao, M.S.; Kerr, K.M. PD-L1 immunohistochemistry assays for lung cancer: Results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J. Thorac. Oncol., 2017, 12(2), 208-222.
[http://dx.doi.org/10.1016/j.jtho.2016.11.2228] [PMID: 27913228]
[9]
Carbone, D.P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; van den Heuvel, M.M.; Ciuleanu, T-E.; Badin, F.; Ready, N.; Hiltermann, T.J.N.; Nair, S.; Juergens, R.; Peters, S.; Minenza, E.; Wrangle, J.M.; Rodriguez-Abreu, D.; Borghaei, H.; Blumenschein, G.R., Jr; Villaruz, L.C.; Havel, L.; Krejci, J.; Corral Jaime, J.; Chang, H.; Geese, W.J.; Bhagavatheeswaran, P.; Chen, A.C.; Socinski, M.A. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N. Engl. J. Med., 2017, 376(25), 2415-2426.
[http://dx.doi.org/10.1056/NEJMoa1613493] [PMID: 28636851]
[10]
Middleton, G.; Brock, K.; Savage, J.; Mant, R.; Summers, Y.; Connibear, J.; Shah, R.; Ottensmeier, C.; Shaw, P.; Lee, S.M.; Popat, S.; Barrie, C.; Barone, G.; Billingham, L. Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): A single arm, phase 2 trial. Lancet Respir. Med., 2020, 8(9), 895-904.
[http://dx.doi.org/10.1016/S2213-2600(20)30033-3] [PMID: 32199466]
[11]
Facchinetti, F.; Mazzaschi, G.; Barbieri, F.; Passiglia, F.; Mazzoni, F.; Berardi, R.; Proto, C.; Cecere, F.L.; Pilotto, S.; Scotti, V.; Rossi, S.; Del Conte, A.; Vita, E.; Bennati, C.; Ardizzoni, A.; Cerea, G.; Migliorino, M.R.; Sala, E.; Camerini, A.; Bearz, A.; De Carlo, E.; Zanelli, F.; Guaitoli, G.; Garassino, M.C.; Ciccone, L.P.; Sartori, G.; Toschi, L.; Dall’Olio, F.G.; Landi, L. Pizzutilo, E.G.; Bartoli, G.; Baldessari, C.; Novello, S.; Bria, E.; Cortinovis, D.L.; Rossi, G.; Rossi, A.; Banna, G.L.; Camisa, R.; Di Maio, M.; Tiseo, M. First-line pembrolizumab in advanced non-small cell lung cancer patients with poor performance status. Eur. J. Cancer, 2020, 130, 155-167.
[http://dx.doi.org/10.1016/j.ejca.2020.02.023] [PMID: 32220780]
[12]
Aguilar, E.J.; Ricciuti, B.; Gainor, J.F.; Kehl, K.L.; Kravets, S.; Dahlberg, S.; Nishino, M.; Sholl, L.M.; Adeni, A.; Subegdjo, S.; Khosrowjerdi, S.; Peterson, R.M.; Digumarthy, S.; Liu, C.; Sauter, J.; Rizvi, H.; Arbour, K.C.; Carter, B.W.; Heymach, J.V.; Altan, M.; Hellmann, M.D.; Awad, M.M. Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Ann. Oncol., 2019, 30(10), 1653-1659.
[http://dx.doi.org/10.1093/annonc/mdz288] [PMID: 31435660]
[13]
Gainor, J.F.; Rizvi, H.; Jimenz Aguilar, E.; Skoulidis, F.; Yeap, B.Y.; Naidoo, J.; Khosrowjerdi, S.; Mooradian, M.; Lydon, C.; Illei, P.; Zhang, J.; Peterson, R.; Ricciuti, B.; Nishino, M.; Zhang, J.; Roth, J.A.; Grishman, J.; Anderson, D.; Little, B.P.; Carter, B.W.; Arbour, K.; Sauter, J.L.; Mino-Kenudson, M.; Heymach, J.V.; Digumarthy, S.; Shaw, A.T.; Awad, M.M.; Hellmann, M.D. Clinical activity of programmed cell death 1 (PDL-1) blockade in never, light, and heavy smokers with non-small-cell lung cancer and PD-L1 expression > 50%. Ann. Oncol., 2020, 31(3), 404-411.
[http://dx.doi.org/10.1016/j.annonc.2019.11.015] [PMID: 32067682]
[14]
Gandhi, L.; Rodríguez-Abreu, D.; Gadgeel, S.; Esteban, E.; Felip, E.; De Angelis, F.; Domine, M.; Clingan, P.; Hochmair, M.J.; Powell, S.F.; Cheng, S.Y.; Bischoff, H.G.; Peled, N.; Grossi, F.; Jennens, R.R.; Reck, M.; Hui, R.; Garon, E.B.; Boyer, M.; Rubio-Viqueira, B.; Novello, S.; Kurata, T.; Gray, J.E.; Vida, J.; Wei, Z.; Yang, J.; Raftopoulos, H.; Pietanza, M.C.; Garassino, M.C. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N. Engl. J. Med., 2018, 378(22), 2078-2092.
[http://dx.doi.org/10.1056/NEJMoa1801005] [PMID: 29658856]
[15]
Paz-Ares, L.; Luft, A.; Vicente, D.; Tafreshi, A.; Gümüş, M.; Mazières, J.; Hermes, B.; Çay Şenler, F.; Csőszi, T.; Fülöp, A.; Rodríguez-Cid, J.; Wilson, J.; Sugawara, S.; Kato, T.; Lee, K.H.; Cheng, Y.; Novello, S.; Halmos, B.; Li, X.; Lubiniecki, G.M.; Piperdi, B.; Kowalski, D.M. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N. Engl. J. Med., 2018, 379(21), 2040-2051.
[http://dx.doi.org/10.1056/NEJMoa1810865] [PMID: 30280635]
[16]
Baldini, E.; Lunghi, A.; Cortesi, E.; Turci, D.; Signorelli, D.; Stati, V.; Melotti, B.; Ricciuti, B.; Frassoldati, A.; Romano, G.; Ceresoli, G.L.; Illiano, A.; Verderame, F.; Fasola, G.; Ricevuto, E.; Marchetti, P.; Pinto, C.; Cartenì, G.; Scotti, V.; Tibaldi, C.; Fioretto, L.; Giannarelli, D. Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab: The Italian NSCLC expanded access program. Lung Cancer, 2020, 140, 59-64.
[http://dx.doi.org/10.1016/j.lungcan.2019.12.014] [PMID: 31881412]
[17]
Qiao, M.; Zhou, F.; Hou, L.; Li, X.; Zhao, C.; Jiang, T.; Gao, G.; Su, C. C.; Wu, C.; Shengxiang Ren, S; Zhou, C. Efficacy of immune-check point inhibitors in advanced non-small-cell lung cancer patients with different metastases. Ann. Transl. Med., 2021, 9, 34-47.
[http://dx.doi.org/10.21037/atm-20-1471] [PMID: 33553327]
[18]
Tumeh, P.C.; Hellmann, M.D.; Hamid, O.; Tsai, K.K.; Loo, K.L.; Gubens, M.A.; Rosenblum, M.; Harview, C.L.; Taube, J.M.; Handley, N.; Khurana, N.; Nosrati, A.; Krummel, M.F.; Tucker, A.; Sosa, E.V.; Sanchez, P.J.; Banayan, N.; Osorio, J.C.; Nguyen-Kim, D.L.; Chang, J.; Shintaku, I.P.; Boasberg, P.D.; Taylor, E.J.; Munster, P.N.; Algazi, A.P.; Chmielowski, B.; Dummer, R.; Grogan, T.R.; Elashoff, D.; Hwang, J.; Goldinger, S.M.; Garon, E.B.; Pierce, R.H.; Daud, A. Liver metastases and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC. Cancer Immunol. Res., 2017, 5(5), 417-424.
[http://dx.doi.org/10.1158/2326-6066.CIR-16-0325] [PMID: 28411193]
[19]
Gadgeel, S.; Rodríguez-Abreu, D.; Speranza, G.; Esteban, E.; Felip, E.; Dómine, M.; Hui, R.; Hochmair, M.J.; Clingan, P.; Powell, S.F.; Cheng, S.Y.; Bischoff, H.G.; Peled, N.; Grossi, F.; Jennens, R.R.; Reck, M.; Garon, E.B.; Novello, S.; Rubio-Viqueira, B.; Boyer, M.; Kurata, T.; Gray, J.E.; Yang, J.; Bas, T.; Pietanza, M.C.; Garassino, M.C. Updated analysis from KEYNOTE-189: Pembrolizumab or placebo plus pemetrexed and platinum for previously untreated metastatic nonsquamous non-small-cell lung cancer. J. Clin. Oncol., 2020, 38(14), 1505-1517.
[http://dx.doi.org/10.1200/JCO.19.03136] [PMID: 32150489]
[20]
West, H.; McCleod, M.; Hussein, M.; Morabito, A.; Rittmeyer, A.; Conter, H.J.; Kopp, H.G.; Daniel, D.; McCune, S.; Mekhail, T.; Zer, A.; Reinmuth, N.; Sadiq, A.; Sandler, A.; Lin, W.; Ochi Lohmann, T.; Archer, V.; Wang, L.; Kowanetz, M.; Cappuzzo, F. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): A multicentre, randomised, open-label, phase 3 trial. Lancet Oncol., 2019, 20(7), 924-937.
[http://dx.doi.org/10.1016/S1470-2045(19)30167-6] [PMID: 31122901]
[21]
Reck, M.; Mok, T.S.K.; Nishio, M.; Jotte, R.M.; Cappuzzo, F.; Orlandi, F.; Stroyakovskiy, D.; Nogami, N.; Rodríguez-Abreu, D.; Moro-Sibilot, D.; Thomas, C.A.; Barlesi, F.; Finley, G.; Lee, A.; Coleman, S.; Deng, Y.; Kowanetz, M.; Shankar, G.; Lin, W.; Socinski, M.A. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): Key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir. Med., 2019, 7(5), 387-401.
[http://dx.doi.org/10.1016/S2213-2600(19)30084-0] [PMID: 30922878]
[22]
Socinski, M.A.; Jotte, R.M.; Cappuzzo, F.; Orlandi, F.; Stroyakovskiy, D.; Nogami, N.; Rodríguez-Abreu, D.; Moro-Sibilot, D.; Thomas, C.A.; Barlesi, F.; Finley, G.; Kelsch, C.; Lee, A.; Coleman, S.; Deng, Y.; Shen, Y.; Kowanetz, M.; Lopez-Chavez, A.; Sandler, A.; Reck, M. Atezolizumab for first line treatment of metastatic nonsquamous NSCLC. N. Engl. J. Med., 2018, 378(24), 2288-2301.
[http://dx.doi.org/10.1056/NEJMoa1716948] [PMID: 29863955]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy