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Combinatorial Chemistry & High Throughput Screening


ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Review Article

Efficacy and Safety of Addition of Anti-PD1 to Chemotherapy in Treatment of Non-Small Cell Lung Cancer

Author(s): Chu-Hui Ru and Yan-Bing Zhuang*

Volume 21, Issue 10, 2018

Page: [711 - 717] Pages: 7

DOI: 10.2174/1386207322666190125150921

Price: $65


Background: Patients with previously treated non-small-cell lung cancer (NSCLC) have limited treatment options. A novel treatment based on programmed death 1 (PD-1)/programed death ligand 1 (PD-L1) inhibitors has emerged as promising therapeutic options for advanced NSCLC. We assessed oncological outcomes of PD-L1 antibody versus docetaxel in previously treated NSCLC.

Objectives: The purpose of this meta-analysis was to analyse the oncological outcomes of anti-PD1 to chemotherapy in the treatment of non-small-cell lung cancer.

Results: Overall survival (OR=0.68,95%CI=0.61-0.75, P<0.00001) and progression-free survival (OR=0.84,95%CI=0.77-0.92, P=0.0002) were longer with anti-PD1 than with docetaxel in NSCLC. Anti-PD1 was associated with even greater objective response rate than docetaxel (OR=1.61,95%CI=1.16-2.24, P=0.004). Treatment-related adverse events of grade 3-5 did favor anti-PD1 over docetaxel (OR=0.21,95%CI=0.10-0.42, P<0.00001).

Conclusions: Among patients with advanced NSCLC, we found that there was a superior survival benefit and with a favorable safety profile with anti-PD1 than with docetaxel. More large-scale randomized controlled trials are needed to identify relevant biomarkers that have an effect on predicting the population that would most likely benefit from PD-1/PD-L1 for pretreated advanced NSCLC patients.

Keywords: Non-small-cell lung cancer, programmed death 1, programmed death ligand 1, meta-analysis, chemotherapy, anti- PD1.

Chae, Y.K.; Pan, A.; Davis, A.A.; Mohindra, N.; Matsangou, M.; Villaflor, V.; Giles, F. Recent Advances and Future Strategies for Immune-Checkpoint Inhibition in Small-Cell Lung Cancer. Clin. Lung Cancer, 2017, 18(2), 132-140.
Zappa, C.; Mousa, S.A. Non-small cell lung cancer: current treatment and future advances. Transl. Lung Cancer Res., 2016, 5(3), 288-300.
Kazandjian, D.; Suzman, D.L.; Blumenthal, G.; Mushti, S.; He, K.; Libeg, M.; Keegan, P.; Pazdur, R. FDA Approval Summary: Nivolumab for the Treatment of Metastatic Non-Small Cell Lung Cancer With Progression On or After Platinum-Based Chemotherapy. Oncologist, 2016, 21(5), 634-642.
Paramanathan, A.; Solomon, B.; Collins, M.; Franco, M.; Kofoed, S.; Francis, H.; Ball, D.; Mileshkin, L. Patients treated with platinum-doublet chemotherapy for advanced non--small-cell lung cancer have inferior outcomes if previously treated with platinum-based chemoradiation. Clin. Lung Cancer, 2013, 14(5), 508-512.
Lu, S. Cheng, Y.; Zhou, C.C.; Wang, J.; Chih-Hsin Yang, J.; Zhang, P.H.; Zhang, X.Q.; Wang, X.; Orlando, M.; Wu, Y.L. Meta-Analysis of First-Line Pemetrexed Plus Platinum Treatment in Compared to Other Platinum-Based Doublet Regimens in Elderly East Asian Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer. Clin. Lung Cancer, 2016, 17(5), e103-e112.
He, X.; Wang, J.; Li, Y. Efficacy and safety of docetaxel for advanced non-small-cell lung cancer: a meta-analysis of Phase III randomized controlled trials. OncoTargets Ther., 2015, 8, 2023-2031.
Fossella, F.V.; DeVore, R.; Kerr, R.N.; Crawford, J.; Natale, R.R.; Dunphy, F.; Kalman, L.; Miller, V.; Lee, J.S.; Moore, M.; Gandara, D.; Karp, D.; Vokes, E.; Kris, M.; Kim, Y.; Gamza, F.; Hammershaimb, L. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J. Clin. Oncol., 2000, 18(12), 2354-2362.
Shepherd, F.A.; Dancey, J.; Ramlau, R.; Mattson, K.; Gralla, R.; O’Rourke, M.; Levitan, N.; Gressot, L.; Vincent, M.; Burkes, R.; Coughlin, S.; Kim, Y.; Berille, J. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J. Clin. Oncol., 2000, 18(10), 2095-2103.
Lopes, G. The role of biomarkers in improving clinical trial success: A study of 1,079 oncology drugs. J. Clin. Oncol., 2015, 33, e17804-e17804.
Zhou, C.; Wu, Y.L.; Chen, G.; Feng, J.; Liu, X.Q.; Wang, C.; Zhang, S.; Wang, J.; Zhou, S.; Ren, S.; Lu, S.; Zhang, L.; Hu, C.; Hu, C.; Luo, Y.; Chen, L.; Ye, M.; Huang, J.; Zhi, X.; Zhang, Y.; Xiu, Q.; Ma, J.; Zhang, L.; You, C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann. Oncol., 2015, 26(9), 1877-1883.
Sequist, L.V.; Yang, J.C.; Yamamoto, N.; O’Byrne, K.; Hirsh, V.; Mok, T.; Geater, S.L.; Orlov, S.; Tsai, C.M.; Boyer, M.; Su, W.C.; Bennouna, J.; Kato, T.; Gorbunova, V.; Lee, K.H.; Shah, R.; Massey, D.; Zazulina, V.; Shahidi, M.; Schuler, M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J. Clin. Oncol., 2013, 31(27), 3327-3334.
Wu, Y-L.; Zhou, C.; Hu, C.P.; Feng, J.; Lu, S.; Huang, Y.; Li, W.; Hou, M.; Shi, J.H.; Lee, K.Y.; Xu, C.R.; Massey, D.; Kim, M.; Shi, Y.; Geater, S.L. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol., 2014, 15(2), 213-222.
Mok, T.S.; Wu, Y.L.; Thongprasert, S.; Yang, C.H.; Chu, D.T.; Saijo, N.; Sunpaweravong, P.; Han, B.; Margono, B.; Ichinose, Y.; Nishiwaki, Y.; Ohe, Y.; Yang, J.J.; Chewaskulyong, B.; Jiang, H.; Duffield, E.L.; Watkins, C.L.; Armour, A.A.; Fukuoka, M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med., 2009, 361(10), 947-957.
Domingues, D.; Turner, A.; Silva, M.D.; Marques, D.S.; Mellidez, J.C.; Wannesson, L.; Mountzios, G.; de Mello, R.A. Immunotherapy and lung cancer: current developments and novel targeted therapies. Immunotherapy, 2014, 6(11), 1221-1235.
Chen, D.S.; Irving, B.A.; Hodi, F.S. Molecular pathways: next-generation immunotherapy--inhibiting programmed death-ligand 1 and programmed death-1. Clin. Cancer Res., 2012, 18(24), 6580-6587.
Goldberg, S.B.; Gettinger, S.N.; Mahajan, A.; Chiang, A.C.; Herbst, R.S.; Sznol, M.; Tsiouris, A.J.; Cohen, J.; Vortmeyer, A.; Jilaveanu, L.; Yu, J.; Hegde, U.; Speaker, S.; Madura, M.; Ralabate, A.; Rivera, A.; Rowen, E.; Gerrish, H.; Yao, X.; Chiang, V.; Kluger, H.M. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol., 2016, 17(7), 976-983.
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.
Fehrenbacher, L.; Spira, A.; Ballinger, M.; Kowanetz, M.; Vansteenkiste, J.; Mazieres, J.; Park, K.; Smith, D.; Artal-Cortes, A.; Lewanski, C.; Braiteh, F.; Waterkamp, D.; He, P.; Zou, W.; Chen, D.S.; Yi, J.; Sandler, A.; Rittmeyer, A. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet, 2016, 387(10030), 1837-1846.
Ettinger, D.S.; Wood, D.E.; Akerley, W.; Bazhenova, L.A.; Borghaei, H.; Camidge, D.R.; Cheney, R.T.; Chirieac, L.R.; D’Amico, T.A.; Demmy, T.L.; Dilling, T.J.; Dobelbower, M.C.; Govindan, R.; Grannis, F.W., Jr; Horn, L.; Jahan, T.M.; Komaki, R.; Krug, L.M.; Lackner, R.P.; Lanuti, M.; Lilenbaum, R.; Lin, J.; Loo, B.W., Jr; Martins, R.; Otterson, G.A.; Patel, J.D.; Pisters, K.M.; Reckamp, K.; Riely, G.J.; Rohren, E.; Schild, S.E.; Shapiro, T.A.; Swanson, S.J.; Tauer, K.; Yang, S.C.; Gregory, K.; Hughes, M. Non-Small Cell Lung Cancer, Version 6.2015. J. Natl. Compr. Canc. Netw., 2015, 13(5), 515-524.
Kim, E.S.; Hirsh, V.; Mok, T.; Socinski, M.A.; Gervais, R.; Wu, Y.L.; Li, L.Y.; Watkins, C.L.; Sellers, M.V.; Lowe, E.S.; Sun, Y.; Liao, M.L.; Osterlind, K.; Reck, M.; Armour, A.A.; Shepherd, F.A.; Lippman, S.M.; Douillard, J.Y. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet, 2008, 372(9652), 1809-1818.
Hanna, N.; Shepherd, F.A.; Fossella, F.V.; Pereira, J.R.; De Marinis, F.; von Pawel, J.; Gatzemeier, U.; Tsao, T.C.; Pless, M.; Muller, T.; Lim, H.L.; Desch, C.; Szondy, K.; Gervais, R. Shaharyar; Manegold, C.; Paul, S.; Paoletti, P.; Einhorn, L.; Bunn, P.A., Jr Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J. Clin. Oncol., 2004, 22(9), 1589-1597.
Tierney, J.F.; Stewart, L.A.; Ghersi, D.; Burdett, S.; Sydes, M.R. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 2007, 8, 16.
Higgins, J.P.T.; Thompson, S.G. Quantifying heterogeneity in a meta-analysis. Stat. Med., 2002, 21(11), 1539-1558.
Higgins, J.P.T.; Thompson, S.G.; Deeks, J.J.; Altman, D.G. Measuring inconsistency in meta-analyses. BMJ, 2003, 327(7414), 557-560.
Borghaei, H.; Paz-Ares, L.; Horn, L.; Spigel, D.R.; Steins, M.; Ready, N.E.; Chow, L.Q.; Vokes, E.E.; Felip, E.; Holgado, E.; Barlesi, F.; Kohlhäufl, M.; Arrieta, O.; Burgio, M.A.; Fayette, J.; Lena, H.; Poddubskaya, E.; Gerber, D.E.; Gettinger, S.N.; Rudin, C.M.; Rizvi, N.; Crinò, L.; Blumenschein, G.R., Jr; Antonia, S.J.; Dorange, C.; Harbison, C.T.; Graf Finckenstein, F.; Brahmer, J.R. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N. Engl. J. Med., 2015, 373(17), 1627-1639.
Brahmer, J.; Reckamp, K.L.; Baas, P.; Crinò, L.; Eberhardt, W.E.; Poddubskaya, E.; Antonia, S.; Pluzanski, A.; Vokes, E.E.; Holgado, E.; Waterhouse, D.; Ready, N.; Gainor, J.; Arén Frontera, O.; Havel, L.; Steins, M.; Garassino, M.C.; Aerts, J.G.; Domine, M.; Paz-Ares, L.; Reck, M.; Baudelet, C.; Harbison, C.T.; Lestini, B.; Spigel, D.R. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N. Engl. J. Med., 2015, 373(2), 123-135.
Garon, E.B.; Ciuleanu, T.E.; Arrieta, O.; Prabhash, K.; Syrigos, K.N.; Goksel, T.; Park, K.; Gorbunova, V.; Kowalyszyn, R.D.; Pikiel, J.; Czyzewicz, G.; Orlov, S.V.; Lewanski, C.R.; Thomas, M.; Bidoli, P.; Dakhil, S.; Gans, S.; Kim, J.H.; Grigorescu, A.; Karaseva, N.; Reck, M.; Cappuzzo, F.; Alexandris, E.; Sashegyi, A.; Yurasov, S.; Pérol, M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet, 2014, 384(9944), 665-673.
Katsuya, Y.; Horinouchi, H.; Asao, T.; Kitahara, S.; Goto, Y.; Kanda, S.; Fujiwara, Y.; Nokihara, H.; Yamamoto, N.; Watanabe, S.; Tsuta, K.; Ohe, Y. Expression of programmed death 1 (PD-1) and its ligand (PD-L1) in thymic epithelial tumors: Impact on treatment efficacy and alteration in expression after chemotherapy. Lung Cancer, 2016, 99, 4-10.
La-Beck, N.M.; Jean, G.W.; Huynh, C.; Alzghari, S.K.; Lowe, D.B. Immune Checkpoint Inhibitors: New Insights and Current Place in Cancer Therapy. Pharmacotherapy, 2015, 35(10), 963-976.
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.

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