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Immunotherapy in Lung Cancer: Are the Promises of Long-Term Benefit Finally Met?

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Immunotherapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1342))

Abstract

Over the last few years, agents targeting immune checkpoints have shown potential to improve therapeutic outcomes in patients with lung cancer in multiple clinical settings. Inhibitors of PD-1/PD-L1 have been approved for the treatment of different types of lung cancer by the FDA either alone or in combination with chemotherapy or other immune checkpoint inhibitors, such as anti-CTLA-4 agents. The introduction of these agents in clinical practice has revolutionized the therapeutic approach to lung cancer, kee** the promises of long-term benefit in selected patient populations. The therapeutic indications of immunotherapy in lung cancer are rapidly growing, and multiple combinations entered clinical practice or are under active development. Furthermore, the quest for a reliable predictive biomarker is still ongoing to overcome the limits of currently approved tests for patients’ selection. In this review, we summarized the current status and progress of anti-PD-1/PD-L1 agents in lung cancer treatment.

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References

  1. Siegel, R. L., Miller, K. D., Fuchs, H. E., & Jemal, A. (2021). Cancer statistics, 2021. CA: a Cancer Journal for Clinicians, 71(1), 7–33. https://doi.org/10.3322/caac.21654

    Article  Google Scholar 

  2. Thomas, A., & Giaccone, G. (2015). Why has active immunotherapy not worked in lung cancer? Annals of Oncology, 26(11), 2213–2220. https://doi.org/10.1093/annonc/mdv323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Pardoll, D. M. (2012). The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews. Cancer, 12(4), 252–264. https://doi.org/10.1038/nrc3239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wei, S. C., Duffy, C. R., & Allison, J. P. (2018). Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discovery, 8(9), 1069–1086. https://doi.org/10.1158/2159-8290.CD-18-0367

    Article  PubMed  Google Scholar 

  5. Russo, A., McCusker, M. G., Scilla, K. A., Arensmeyer, K. E., Mehra, R., Adamo, V., & Rolfo, C. (2020). Immunotherapy in lung Cancer: From a minor god to the Olympus. Advances in Experimental Medicine and Biology, 1244, 69–92. https://doi.org/10.1007/978-3-030-41008-7_4

    Article  CAS  PubMed  Google Scholar 

  6. Rossi, G., Russo, A., Tagliamento, M., Tuzi, A., Nigro, O., Vallome, G., Sini, C., Grassi, M., Dal Bello, M. G., Coco, S., Longo, L., Zullo, L., Tanda, E. T., Dellepiane, C., Pronzato, P., & Genova, C. (2020). Precision medicine for NSCLC in the era of immunotherapy: New biomarkers to select the Most suitable treatment or the Most suitable patient. Cancers (Basel), 12(5). https://doi.org/10.3390/cancers12051125

  7. Weichselbaum, R. R., Liang, H., Deng, L., & Fu, Y.-X. (2017). Radiotherapy and immunotherapy: A beneficial liaison? Nature Reviews. Clinical Oncology, 14(6), 365–379. https://doi.org/10.1038/nrclinonc.2016.211

    Article  CAS  PubMed  Google Scholar 

  8. Galluzzi, L., Humeau, J., Buqué, A., Zitvogel, L., & Kroemer, G. (2020). Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nature Reviews. Clinical Oncology, 17(12), 725–741. https://doi.org/10.1038/s41571-020-0413-z

    Article  PubMed  Google Scholar 

  9. Ribas, A. (2012). Tumor immunotherapy directed at PD-1. The New England Journal of Medicine, 366(26), 2517–2519. https://doi.org/10.1056/NEJMe1205943

    Article  CAS  PubMed  Google Scholar 

  10. Doroshow, D. B., Bhalla, S., Beasley, M. B., Sholl, L. M., Kerr, K. M., Gnjatic, S., Wistuba, I. I., Rimm, D. L., Tsao, M. S., & Hirsch, F. R. (2021). PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nature Reviews. Clinical Oncology. https://doi.org/10.1038/s41571-021-00473-5

  11. 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. (2017). A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung Cancer. JAMA Oncology, 3(8), 1051–1058. https://doi.org/10.1001/jamaoncol.2017.0013

    Article  PubMed  PubMed Central  Google Scholar 

  12. Marchetti, A., Barberis, M., Franco, R., De Luca, G., Pace, M. V., Staibano, S., Volante, M., Buttitta, F., Guerini-Rocco, E., Righi, L., D’antuono, T., Scagliotti, G. V., Pinto, C., De Rosa, G., & Papotti, M. (2017). Multicenter comparison of 22C3 pharm dx (Agilent) and SP263 (Ventana) assays to test PD-L1 expression for NSCLC patients to be treated with immune checkpoint inhibitors. Journal of Thoracic Oncology, 12(11), 1654–1663. https://doi.org/10.1016/j.jtho.2017.07.031

    Article  PubMed  Google Scholar 

  13. 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. (2017). PD-L1 immunohistochemistry assays for lung Cancer: Results from phase 1 of the blueprint PD-L1 IHC assay comparison project. Journal of Thoracic Oncology, 12(2), 208–222. https://doi.org/10.1016/j.jtho.2016.11.2228

    Article  PubMed  Google Scholar 

  14. Tsao, M. S., Kerr, K. M., Kockx, M., Beasley, M.-B., Borczuk, A. C., Botling, J., Bubendorf, L., Chirieac, L., Chen, G., Chou, T.-Y., Chung, J.-H., Dacic, S., Lantuejoul, S., Mino-Kenudson, M., Moreira, A. L., Nicholson, A. G., Noguchi, M., Pelosi, G., Poleri, C., Russell, P. A., Sauter, J., Thunnissen, E., Wistuba, I., Yu, H., Wynes, M. W., Pintilie, M., Yatabe, Y., & Hirsch, F. R. (2018). PD-L1 immunohistochemistry comparability study in real-life clinical samples: Results of blueprint phase 2 project. Journal of Thoracic Oncology, 13(9), 1302–1311. https://doi.org/10.1016/j.jtho.2018.05.013

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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. J., Garrido, M., Lubiniecki, G. M., Shentu, Y., Im, E., Dolled-Filhart, M., & Garon, E. B. (2016). Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet, 387(10027), 1540–1550. https://doi.org/10.1016/S0140-6736(15)01281-7

    Article  CAS  PubMed  Google Scholar 

  16. Russo, A., Franchina, T., Ricciardi, G. R. R., Toscano, G., Schifano, S., Lo Certo, G., Battaglia, A., Pantò, E., Scaffidi Fonti, M., & Adamo, V. (2018). The changing scenario of 1(st) line therapy in non-oncogene addicted NSCLCs in the era of immunotherapy. Critical Reviews in Oncology/Hematology, 130, 1–12. https://doi.org/10.1016/j.critrevonc.2018.06.007

    Article  CAS  PubMed  Google Scholar 

  17. 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. (2016). Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung Cancer. The New England Journal of Medicine, 375(19), 1823–1833. https://doi.org/10.1056/NEJMoa1606774

    Article  CAS  PubMed  Google Scholar 

  18. Herbst, R. S., Giaccone, G., de Marinis, F., Reinmuth, N., Vergnenegre, A., Barrios, C. H., 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, D. R. (2020). Atezolizumab for first-Line treatment of PD-L1-selected patients with NSCLC. The New England Journal of Medicine, 383(14), 1328–1339. https://doi.org/10.1056/NEJMoa1917346

    Article  CAS  PubMed  Google Scholar 

  19. Sezer, A., Kilickap, S., Gümüş, M., Bondarenko, I., Özgüroğlu, M., Gogishvili, M., Turk, H. M., Cicin, I., Bentsion, D., Gladkov, O., Clingan, P., Sriuranpong, V., Rizvi, N., Gao, B., Li, S., Lee, S., McGuire, K., Chen, C.-I., Makharadze, T., Paydas, S., Nechaeva, M., Seebach, F., Weinreich, D. M., Yancopoulos, G. D., Gullo, G., Lowy, I., & Rietschel, P. (2021). 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, 397(10274), 592–604. https://doi.org/10.1016/S0140-6736(21)00228-2

    Article  CAS  PubMed  Google Scholar 

  20. Mok, T. S. K., Wu, Y.-L., Kudaba, I., Kowalski, D. M., Cho, B. C., Turna, H. Z., Castro, G. J., Srimuninnimit, V., Laktionov, K. K., Bondarenko, I., Kubota, K., Lubiniecki, G. M., Zhang, J., Kush, D., & Lopes, G. (2019). 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, 393(10183), 1819–1830. https://doi.org/10.1016/S0140-6736(18)32409-7

    Article  CAS  PubMed  Google Scholar 

  21. Mountzios, G., Remon, J., Novello, S., Blais, N., Califano, R., Cufer, T., Dingemans, A. M., Liu, S. V., Peled, N., Pennell, N. A., Reck, M., Rolfo, C., Tan, D., Vansteenkiste, J., West, H., & Besse, B. (2019). Position of an international panel of lung cancer experts on the decision for expansion of approval for pembrolizumab in advanced non-small-cell lung cancer with a PD-L1 expression level of ≥1% by the USA Food and Drug Administration. Annals of Oncology, 30(11), 1686–1688. https://doi.org/10.1093/annonc/mdz295

    Article  CAS  PubMed  Google Scholar 

  22. Russo, A., De Miguel, P. D., Gunasekaran, M., Scilla, K., Lapidus, R., Cooper, B., Mehra, R., Adamo, V., Malapelle, U., & Rolfo, C. (2019). Liquid biopsy tracking of lung tumor evolutions over time. Expert Review of Molecular Diagnostics, 19(12), 1099–1108. https://doi.org/10.1080/14737159.2020.1680287

    Article  CAS  PubMed  Google Scholar 

  23. Huang, Q., Zhang, H., Hai, J., Socinski, M. A., Lim, E., Chen, H., & Stebbing, J. (2018). Impact of PD-L1 expression, driver mutations and clinical characteristics on survival after anti-PD-1/PD-L1 immunotherapy versus chemotherapy in non-small-cell lung cancer: A meta-analysis of randomized trials. Oncoimmunology, 7(12), e1396403. https://doi.org/10.1080/2162402X.2017.1396403

    Article  PubMed  PubMed Central  Google Scholar 

  24. Russo, A., Russano, M., Franchina, T., Migliorino, M. R., Aprile, G., Mansueto, G., Berruti, A., Falcone, A., Aieta, M., Gelibter, A., Russo, A., Barni, S., Maio, M., Martelli, O., Pantano, F., Iacono, D., Calvetti, L., Quadrini, S., Roca, E., Vasile, E., Imperatori, M., Occhipinti, M., Galvano, A., Petrelli, F., Calabrò, L., Pasquini, G., Intagliata, S., Ricciardi, G. R. R., Tonini, G., Santini, D., & Adamo, V. (2020). Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A large retrospective multicenter study. Advances in Therapy, 37(3), 1145–1155. https://doi.org/10.1007/s12325-020-01229-w

    Article  CAS  PubMed  Google Scholar 

  25. Howlader, N, Noone, A., Krapcho, M., Miller, D., Bishop, K., Kosary, C.L., Yu, M., Ruhl, J., Tatalovich, Z., Mariotto, A., Lewis, D.R., Chen, H.S., Feuer, E.J., Cronin, K.A. (Eds.), SEER Cancer Statistics Review, 1975–2014, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2014/, based on November 2019 SEER data submission, posted to the SEER web site, April 2019.

  26. Pignon, J.-P., Tribodet, H., Scagliotti, G. V., Douillard, J.-Y., Shepherd, F. A., Stephens, R. J., Dunant, A., Torri, V., Rosell, R., Seymour, L., Spiro, S. G., Rolland, E., Fossati, R., Aubert, D., Ding, K., Waller, D., & Le Chevalier, T. (2008). Lung adjuvant cisplatin evaluation: A pooled analysis by the LACE collaborative group. Journal of Clinical Oncology, 26(21), 3552–3559. https://doi.org/10.1200/JCO.2007.13.9030

    Article  PubMed  Google Scholar 

  27. NSCLC collaborative group. (2014). Preoperative chemotherapy for non-small-cell lung cancer: A systematic review and meta-analysis of individual participant data. Lancet, 383(9928), 1561–1571. https://doi.org/10.1016/S0140-6736(13)62159-5

    Article  CAS  Google Scholar 

  28. Burdett, S., Pignon, J. P., Tierney, J., Tribodet, H., Stewart, L., Le Pechoux, C., Aupérin, A., Le Chevalier, T., Stephens, R. J., Arriagada, R., Higgins, J. P. T., Johnson, D. H., Van Meerbeeck, J., Parmar, M. K. B., Souhami, R. L., Bergman, B., Douillard, J.-Y., Dunant, A., Endo, C., Girling, D., Kato, H., Keller, S. M., Kimura, H., Knuuttila, A., Kodama, K., Komaki, R., Kris, M. G., Lad, T., Mineo, T., Piantadosi, S., Rosell, R., Scagliotti, G., Seymour, L. K., Shepherd, F. A., Sylvester, R., Tada, H., Tanaka, F., Torri, V., Waller, D., & Liang, Y. (2015). Adjuvant chemotherapy for resected early-stage non-small cell lung cancer. Cochrane Database of Systematic Reviews, 3, CD011430. https://doi.org/10.1002/14651858.CD011430

    Article  Google Scholar 

  29. Wu, Y.-L., Tsuboi, M., He, J., John, T., Grohe, C., Majem, M., Goldman, J. W., Laktionov, K., Kim, S.-W., Kato, T., Vu, H.-V., Lu, S., Lee, K.-Y., Akewanlop, C., Yu, C.-J., de Marinis, F., Bonanno, L., Domine, M., Shepherd, F. A., Zeng, L., Hodge, R., Atasoy, A., Rukazenkov, Y., & Herbst, R. S. (2020). Osimertinib in resected EGFR-mutated non-small-cell lung Cancer. The New England Journal of Medicine, 383(18), 1711–1723. https://doi.org/10.1056/NEJMoa2027071

    Article  CAS  PubMed  Google Scholar 

  30. Ahn, M.-J., Park, S., Jung, H. A., Cho, J. H., Sun, J.-M., Lee, S.-H., Choi, Y. S., Ahn, J. S., Kim, J., Park, K., Zo, J. I., Shim, Y. M., Kim, K. H., Shin, E.-C., & Kim, H. K. (2019). Phase II, prospective single-arm study of adjuvant pembrolizumab in N2 positive non-small cell lung cancer (NSCLC) treated with neoadjuvant concurrent chemoradiotherapy followed by curative resection: Preliminary results. JCO, 37(15_suppl), 8520–8520. https://doi.org/10.1200/JCO.2019.37.15_suppl.8520

    Article  Google Scholar 

  31. Forde, P. M., Chaft, J. E., Smith, K. N., Anagnostou, V., Cottrell, T. R., Hellmann, M. D., Zahurak, M., Yang, S. C., Jones, D. R., Broderick, S., Battafarano, R. J., Velez, M. J., Rekhtman, N., Olah, Z., Naidoo, J., Marrone, K. A., Verde, F., Guo, H., Zhang, J., Caushi, J. X., Chan, H. Y., Sidhom, J.-W., Scharpf, R. B., White, J., Gabrielson, E., Wang, H., Rosner, G. L., Rusch, V., Wolchok, J. D., Merghoub, T., Taube, J. M., Velculescu, V. E., Topalian, S. L., Brahmer, J. R., & Pardoll, D. M. (2018). Neoadjuvant PD-1 blockade in Resectable lung Cancer. The New England Journal of Medicine, 378(21), 1976–1986. https://doi.org/10.1056/NEJMoa1716078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lee, J., Chaft, J., Nicholas, A., Patterson, A., Waqar, S., Toloza, E., Haura, E., Raz, D., Reckamp, K., Merritt, R., Owen, D., Finley, D., Mcnamee, C., Blasberg, J., Garon, E., Mitchell, J., Doebele, R., Baciewicz, F., Nagasaka, M., Pass, H., Schulze, K., Phan, S., Johnson, A., Bunn, P., Johnson, B., Kris, M., Kwiatkowski, D., Wistuba, I., Carbone, D., & Rusch, V. (2021). PS01.05 surgical and clinical outcomes with neoadjuvant Atezolizumab in Resectable stage IB–IIIB NSCLC: LCMC3 trial primary analysis. Journal of Thoracic Oncology, 16(3), S59–S61. https://doi.org/10.1016/j.jtho.2021.01.320

    Article  Google Scholar 

  33. Cascone, T., William, W. N. J., Weissferdt, A., Leung, C. H., Lin, H. Y., Pataer, A., Godoy, M. C. B., Carter, B. W., Federico, L., Reuben, A., Khan, M. A. W., Dejima, H., Francisco-Cruz, A., Parra, E. R., Solis, L. M., Fujimoto, J., Tran, H. T., Kalhor, N., Fossella, F. V., Mott, F. E., Tsao, A. S., Blumenschein, G. J., Le, X., Zhang, J., Skoulidis, F., Kurie, J. M., Altan, M., Lu, C., Glisson, B. S., Byers, L. A., Elamin, Y. Y., Mehran, R. J., Rice, D. C., Walsh, G. L., Hofstetter, W. L., Roth, J. A., Antonoff, M. B., Kadara, H., Haymaker, C., Bernatchez, C., Ajami, N. J., Jenq, R. R., Sharma, P., Allison, J. P., Futreal, A., Wargo, J. A., Wistuba, I. I., Swisher, S. G., Lee, J. J., Gibbons, D. L., Vaporciyan, A. A., Heymach, J. V., & Sepesi, B. (2021). Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: The phase 2 randomized NEOSTAR trial. Nature Medicine, 27(3), 504–514. https://doi.org/10.1038/s41591-020-01224-2

    Article  CAS  PubMed  Google Scholar 

  34. Provencio, M., Nadal, E., Insa, A., García-Campelo, M. R., Casal-Rubio, J., Dómine, M., Majem, M., Rodríguez-Abreu, D., Martínez-Martí, A., De Castro, C. J., Cobo, M., López Vivanco, G., Del Barco, E., Bernabé Caro, R., Viñolas, N., Barneto Aranda, I., Viteri, S., Pereira, E., Royuela, A., Casarrubios, M., Salas Antón, C., Parra, E. R., Wistuba, I., Calvo, V., Laza-Briviesca, R., Romero, A., Massuti, B., & Cruz-Bermúdez, A. (2020). Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): An open-label, multicentre, single-arm, phase 2 trial. The Lancet Oncology, 21(11), 1413–1422. https://doi.org/10.1016/S1470-2045(20)30453-8

    Article  CAS  PubMed  Google Scholar 

  35. Shu, C. A., Gainor, J. F., Awad, M. M., Chiuzan, C., Grigg, C. M., Pabani, A., Garofano, R. F., Stoopler, M. B., Cheng, S. K., White, A., Lanuti, M., D’Ovidio, F., Bacchetta, M., Sonett, J. R., Saqi, A., & Rizvi, N. A. (2020). Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: An open-label, multicentre, single-arm, phase 2 trial. The Lancet Oncology, 21(6), 786–795. https://doi.org/10.1016/S1470-2045(20)30140-6

    Article  CAS  PubMed  Google Scholar 

  36. Ready, N., Tong, B., Clarke, J., Gu, L., Wigle, D., Dragnev, K., Sporn, T., Stinchcombe, T., & D’Amico, T. (2019). P2.04-89 neoadjuvant Pembrolizumab in early stage Non-Small Cell Lung Cancer (NSCLC): Toxicity, efficacy, and surgical outcomes. Journal of Thoracic Oncology, 14(10), S745. https://doi.org/10.1016/j.jtho.2019.08.1594

    Article  Google Scholar 

  37. Bar, J., Urban, D., Ofek, E., Ackerstein, A., Redinsky, I., Golan, N., Kamer, I., Simansky, D., Onn, A., Raskin, S., Shulimzon, T., Peled, M., Zeitlin, N., Halparin, S., Jurkowicz, M., Abukhalil, R., Perelman, M., & Ben-Nun, A. (2019). Neoadjuvant pembrolizumab (Pembro) for early stage non-small cell lung cancer (NSCLC): Updated report of a phase I study, MK3475-223. JCO, 37(15_suppl), 8534–8534. https://doi.org/10.1200/JCO.2019.37.15_suppl.8534

    Article  Google Scholar 

  38. Gao, S., Li, N., Gao, S., Xue, Q., Ying, J., Wang, S., Tao, X., Zhao, J., Mao, Y., Wang, B., Shao, K., Lei, W., Wang, D., Lv, F., Zhao, L., Zhang, F., Zhao, Z., Su, K., Tan, F., Gao, Y., Sun, N., Wu, D., Yu, Y., Ling, Y., Wang, Z., Duan, C., Tang, W., Zhang, L., He, S., Wu, N., Wang, J., & He, J. (2020). Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC. Journal of Thoracic Oncology, 15(5), 816–826. https://doi.org/10.1016/j.jtho.2020.01.017

    Article  CAS  PubMed  Google Scholar 

  39. Wislez, M., Mazieres, J., Lavole, A., Zalcman, G., Carre, O., Egenod, T., Caliandro, R., Gervais, R., Jeannin, G., Molinier, O., Massiani, M. A., Langlais, A., Morin, F., Le Pimpec, B. F., Brouchet, L., Assouad, J., Milleron, B., Damotte, D., Antoine, M., & Westeel, V. (2020). 1214O neoadjuvant durvalumab in resectable non-small cell lung cancer (NSCLC): Preliminary results from a multicenter study (IFCT-1601 IONESCO). Annals of Oncology, 31, S794. https://doi.org/10.1016/j.annonc.2020.08.1416

    Article  Google Scholar 

  40. Besse, B., Adam, J., Cozic, N., Chaput-Gras, N., Planchard, D., Mezquita, L., Masip, J. R., Lavaud, P., Naltet, C., Gazzah, A., Thomas de Montpreville, V., Ghigna, M.-R., Mussot, S., Fadel, E., Mabille, L., Duchemann, B., Barlesi, F., Soria, J.-C., Caramella, C., & Mercier, O. (2020). 1215O – SC Neoadjuvant atezolizumab (A) for resectable non-small cell lung cancer (NSCLC): Results from the phase II PRINCEPS trial. Annals of Oncology, 31, S794–S795. https://doi.org/10.1016/j.annonc.2020.08.1417

    Article  Google Scholar 

  41. Zinner, R., Axelrod, R., Solomides, C. C., Cowan, S., Leiby, B., Bhatia, A. K., Sundermeyer, M. L., Hooper, D. C., Harshyne, L., Lu-Yao, G. L., Quereda-Bernabeu, B. C., Whang, S. C., OHara, S. C., Vernau, D. C., Werner-Wasik, M., Lu, B., Johnson, J. M., Scott, W. C., Argiris, A., & Evans, N. R. (2020). Neoadjuvant nivolumab (N) plus cisplatin (C)/pemetrexed (P) or cisplatin/gemcitabine (G) in resectable NSCLC. JCO, 38(15_suppl), 9051–9051. https://doi.org/10.1200/JCO.2020.38.15_suppl.9051

    Article  Google Scholar 

  42. Yang, C.-F. J., McSherry, F., Mayne, N. R., Wang, X., Berry, M. F., Tong, B., Harpole, D. H. J., D’Amico, T. A., Christensen, J. D., Ready, N. E., & Klapper, J. A. (2018). Surgical outcomes after neoadjuvant chemotherapy and Ipilimumab for non-small cell lung Cancer. The Annals of Thoracic Surgery, 105(3), 924–929. https://doi.org/10.1016/j.athoracsur.2017.09.030

    Article  PubMed  Google Scholar 

  43. Rothschild, S., Zippelius, A., Eboulet, E. I., Savic, S., Betticher, D. C., Bettini, A., Frueh, M., Joerger, M., Britschgi, C., Peters, S., Mark, M. T., Ochsenbein, A., Janthur, W. D., Waibel, C., Mach, N., Gonzalez, M., Froesch, P., Godar, G., Rusterholz, C., & Pless, M. (2020). SAKK 16/14: Anti-PD-L1 antibody durvalumab in addition to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small cell lung cancer (NSCLC)—A multicenter single-arm phase II trial. JCO, 38(15_suppl), 9016–9016. https://doi.org/10.1200/JCO.2020.38.15_suppl.9016

    Article  Google Scholar 

  44. Aupérin, A., Le Péchoux, C., Pignon, J. P., Koning, C., Jeremic, B., Clamon, G., Einhorn, L., Ball, D., Trovo, M. G., Groen, H. J. M., Bonner, J. A., Le Chevalier, T., & Arriagada, R. (2006). Concomitant radio-chemotherapy based on platin compounds in patients with locally advanced non-small cell lung cancer (NSCLC): A meta-analysis of individual data from 1764 patients. Annals of Oncology, 17(3), 473–483. https://doi.org/10.1093/annonc/mdj117

    Article  PubMed  Google Scholar 

  45. Aupérin, A., Le Péchoux, C., Rolland, E., Curran, W. J., Furuse, K., Fournel, P., Belderbos, J., Clamon, G., Ulutin, H. C., Paulus, R., Yamanaka, T., Bozonnat, M.-C., Uitterhoeve, A., Wang, X., Stewart, L., Arriagada, R., Burdett, S., & Pignon, J.-P. (2010). Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. Journal of Clinical Oncology, 28(13), 2181–2190. https://doi.org/10.1200/JCO.2009.26.2543

    Article  CAS  PubMed  Google Scholar 

  46. Antonia, S. J., Villegas, A., Daniel, D., Vicente, D., Murakami, S., Hui, R., Kurata, T., Chiappori, A., Lee, K. H., de Wit, M., Cho, B. C., Bourhaba, M., Quantin, X., Tokito, T., Mekhail, T., Planchard, D., Kim, Y.-C., Karapetis, C. S., Hiret, S., Ostoros, G., Kubota, K., Gray, J. E., Paz-Ares, L., de Castro, C. J., Faivre-Finn, C., Reck, M., Vansteenkiste, J., Spigel, D. R., Wadsworth, C., Melillo, G., Taboada, M., Dennis, P. A., & Özgüroğlu, M. (2018). Overall survival with Durvalumab after Chemoradiotherapy in stage III NSCLC. The New England Journal of Medicine, 379(24), 2342–2350. https://doi.org/10.1056/NEJMoa1809697

    Article  CAS  PubMed  Google Scholar 

  47. Gray, J. E., Villegas, A., Daniel, D., Vicente, D., Murakami, S., Hui, R., Kurata, T., Chiappori, A., Lee, K. H., Cho, B. C., Planchard, D., Paz-Ares, L., Faivre-Finn, C., Vansteenkiste, J. F., Spigel, D. R., Wadsworth, C., Taboada, M., Dennis, P. A., Özgüroğlu, M., & Antonia, S. J. (2020). Three-year overall survival with Durvalumab after Chemoradiotherapy in stage III NSCLC-update from PACIFIC. Journal of Thoracic Oncology, 15(2), 288–293. https://doi.org/10.1016/j.jtho.2019.10.002

    Article  CAS  PubMed  Google Scholar 

  48. Faivre-Finn, C., Spigel, D. R., Senan, S., Langer, C., Perez, B. A., Özgüroğlu, M., Daniel, D., Villegas, A., Vicente, D., Hui, R., Murakami, S., Paz-Ares, L., Broadhurst, H., Wadsworth, C., Dennis, P. A., & Antonia, S. J. (2021). Impact of prior chemoradiotherapy-related variables on outcomes with durvalumab in unresectable stage III NSCLC (PACIFIC). Lung Cancer, 151, 30–38. https://doi.org/10.1016/j.lungcan.2020.11.024

    Article  PubMed  Google Scholar 

  49. Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., Pitot, H. C., Hamid, O., Bhatia, S., Martins, R., Eaton, K., Chen, S., Salay, T. M., Alaparthy, S., Grosso, J. F., Korman, A. J., Parker, S. M., Agrawal, S., Goldberg, S. M., Pardoll, D. M., Gupta, A., & Wigginton, J. M. (2012). Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. The New England Journal of Medicine, 366(26), 2455–2465. https://doi.org/10.1056/NEJMoa1200694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., Leming, P. D., Spigel, D. R., Antonia, S. J., Horn, L., Drake, C. G., Pardoll, D. M., Chen, L., Sharfman, W. H., Anders, R. A., Taube, J. M., McMiller, T. L., Xu, H., Korman, A. J., Jure-Kunkel, M., Agrawal, S., McDonald, D., Kollia, G. D., Gupta, A., Wigginton, J. M., & Sznol, M. (2012). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. The New England Journal of Medicine, 366(26), 2443–2454. https://doi.org/10.1056/NEJMoa1200690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Brahmer, J., Reckamp, K. L., Baas, P., Crinò, L., Eberhardt, W. E. 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. (2015). Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung Cancer. The New England Journal of Medicine, 373(2), 123–135. https://doi.org/10.1056/NEJMoa1504627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. 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. J., Antonia, S. J., Dorange, C., Harbison, C. T., Graf Finckenstein, F., & Brahmer, J. R. (2015). Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung Cancer. The New England Journal of Medicine, 373(17), 1627–1639. https://doi.org/10.1056/NEJMoa1507643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Borghaei, H., Gettinger, S., Vokes, E. E., Chow, L. Q. M., Burgio, M. A., de Castro, C. J., Pluzanski, A., Arrieta, O., Frontera, O. A., Chiari, R., Butts, C., Wójcik-Tomaszewska, J., Coudert, B., Garassino, M. C., Ready, N., Felip, E., García, M. A., Waterhouse, D., Domine, M., Barlesi, F., Antonia, S., Wohlleber, M., Gerber, D. E., Czyzewicz, G., Spigel, D. R., Crino, L., Eberhardt, W. E. E., Li, A., Marimuthu, S., & Brahmer, J. (2021). Five-year outcomes from the randomized, phase III trials CheckMate 017 and 057: Nivolumab versus docetaxel in previously treated non-small-cell lung Cancer. Journal of Clinical Oncology, 39(7), 723–733. https://doi.org/10.1200/JCO.20.01605

    Article  PubMed  Google Scholar 

  54. Peters, S., Cappuzzo, F., Horn, L., Paz-Ares, L., Borghaei, H., Barlesi, F., Steins, M., Felip, E., Spigel, D., Dorange, C., Lu, H., Healey, D., Kong Sanchez, T., Bhagavatheeswaran, P., Novotny, J., Jr., Lestini, B., & Brahmer, J. (2017). OA03.05 analysis of early survival in patients with advanced non-squamous NSCLC treated with Nivolumab vs docetaxel in CheckMate 057. Journal of Thoracic Oncology, 12(1), S253. https://doi.org/10.1016/j.jtho.2016.11.241

    Article  Google Scholar 

  55. 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. (2016). Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): A multicentre, open-label, phase 2 randomised controlled trial. Lancet, 387(10030), 1837–1846. https://doi.org/10.1016/S0140-6736(16)00587-0

    Article  CAS  PubMed  Google Scholar 

  56. Rittmeyer, A., Barlesi, F., Waterkamp, D., Park, K., Ciardiello, F., von Pawel, J., Gadgeel, S. M., Hida, T., Kowalski, D. M., Dols, M. C., Cortinovis, D. L., Leach, J., Polikoff, J., Barrios, C., Kabbinavar, F., Frontera, O. A., De Marinis, F., Turna, H., Lee, J.-S., Ballinger, M., Kowanetz, M., He, P., Chen, D. S., Sandler, A., & Gandara, D. R. (2017). Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomised controlled trial. Lancet, 389(10066), 255–265. https://doi.org/10.1016/S0140-6736(16)32517-X

    Article  PubMed  Google Scholar 

  57. Mazieres, J., Rittmeyer, A., Gadgeel, S., Hida, T., Gandara, D. R., Cortinovis, D. L., Barlesi, F., Yu, W., Matheny, C., Ballinger, M., & Park, K. (2021). Atezolizumab versus docetaxel in pretreated patients with NSCLC: Final results from the randomized phase 2 POPLAR and phase 3 OAK clinical trials. Journal of Thoracic Oncology, 16(1), 140–150. https://doi.org/10.1016/j.jtho.2020.09.022

    Article  CAS  PubMed  Google Scholar 

  58. 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. (2015). Pembrolizumab for the treatment of non-small-cell lung cancer. The New England Journal of Medicine, 372(21), 2018–2028. https://doi.org/10.1056/NEJMoa1501824

    Article  PubMed  Google Scholar 

  59. Herbst, R. S., Garon, E. B., Kim, D.-W., Cho, B. C., Perez-Gracia, J. L., Han, J.-Y., Arvis, C. D., Majem, M., Forster, M. D., Monnet, I., Novello, S., Szalai, Z., Gubens, M. A., Su, W.-C., Ceresoli, G. L., Samkari, A., Jensen, E. H., Lubiniecki, G. M., & Baas, P. (2020). Long-term outcomes and retreatment among patients with previously treated, programmed death-ligand 1–positive, advanced non–small-cell lung Cancer in the KEYNOTE-010 study. Journal of Clinical Oncology, 38(14), 1580–1590. https://doi.org/10.1200/JCO.19.02446

    Article  CAS  PubMed  Google Scholar 

  60. Barlesi, F., Vansteenkiste, J., Spigel, D., Ishii, H., Garassino, M., de Marinis, F., Özgüroğlu, M., Szczesna, A., Polychronis, A., Uslu, R., Krzakowski, M., Lee, J.-S., Calabrò, L., Arén Frontera, O., Ellers-Lenz, B., Bajars, M., Ruisi, M., & Park, K. (2018). Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN lung 200): An open-label, randomised, phase 3 study. The Lancet Oncology, 19(11), 1468–1479. https://doi.org/10.1016/S1470-2045(18)30673-9

    Article  CAS  PubMed  Google Scholar 

  61. Tan, P. S., Aguiar, P. J., Haaland, B., & Lopes, G. (2018). Comparative effectiveness of immune-checkpoint inhibitors for previously treated advanced non-small cell lung cancer – a systematic review and network meta-analysis of 3024 participants. Lung Cancer, 115, 84–88. https://doi.org/10.1016/j.lungcan.2017.11.017

    Article  PubMed  Google Scholar 

  62. Lee, C. K., Man, J., Lord, S., Cooper, W., Links, M., Gebski, V., Herbst, R. S., Gralla, R. J., Mok, T., & Yang, J. C.-H. (2018). Clinical and molecular characteristics associated with survival among patients treated with checkpoint inhibitors for advanced non-small cell lung carcinoma: A systematic review and meta-analysis. JAMA Oncology, 4(2), 210–216. https://doi.org/10.1001/jamaoncol.2017.4427

    Article  PubMed  Google Scholar 

  63. 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. (2019). 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. Journal of Clinical Oncology, 37(7), 537–546. https://doi.org/10.1200/JCO.18.00149

    Article  CAS  PubMed  Google Scholar 

  64. 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. (2019). Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Annals of Oncology, 30(10), 1653–1659. https://doi.org/10.1093/annonc/mdz288

    Article  CAS  PubMed  Google Scholar 

  65. 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. J., Villaruz, L. C., Havel, L., Krejci, J., Corral Jaime, J., Chang, H., Geese, W. J., Bhagavatheeswaran, P., Chen, A. C., & Socinski, M. A. (2017). First-Line Nivolumab in stage IV or recurrent non-small-cell lung Cancer. The New England Journal of Medicine, 376(25), 2415–2426. https://doi.org/10.1056/NEJMoa1613493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. 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.-S., 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. (2018). Pembrolizumab plus chemotherapy in metastatic non-small-cell lung Cancer. The New England Journal of Medicine, 378(22), 2078–2092. https://doi.org/10.1056/NEJMoa1801005

    Article  CAS  PubMed  Google Scholar 

  67. 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.-S., 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. (2020). Updated analysis from KEYNOTE-189: Pembrolizumab or placebo plus Pemetrexed and platinum for previously untreated metastatic nonsquamous non-small-cell lung Cancer. Journal of Clinical Oncology, 38(14), 1505–1517. https://doi.org/10.1200/JCO.19.03136

    Article  CAS  PubMed  Google Scholar 

  68. Gray, J., Rodríguez-Abreu, D., Powell, S. F., Hochmair, M. J., Gadgeel, S., Esteban, E., Felip, E., Speranza, G., De Angelis, F., Dómine, M., Cheng, S. Y., Bischoff, H. G., Peled, N., Reck, M., Hui, R., Garon, E. B., Boyer, M., Kurata, T., Yang, J., Jensen, E., Souza, F., & Garassino, M. C. (2021). FP13.02 Pembrolizumab + Pemetrexed-platinum vs Pemetrexed-platinum for metastatic NSCLC: 4-year follow-up from KEYNOTE-189. Journal of Thoracic Oncology, 16(3), S224. https://doi.org/10.1016/j.jtho.2021.01.141

    Article  Google Scholar 

  69. 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. (2018). Pembrolizumab plus chemotherapy for squamous non-small-cell lung Cancer. The New England Journal of Medicine, 379(21), 2040–2051. https://doi.org/10.1056/NEJMoa1810865

    Article  CAS  PubMed  Google Scholar 

  70. Borghaei, H., Langer, C. J., Paz-Ares, L., Rodríguez-Abreu, D., Halmos, B., Garassino, M. C., Houghton, B., Kurata, T., Cheng, Y., Lin, J., Pietanza, M. C., Piperdi, B., & Gadgeel, S. M. (2020). Pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer without tumor PD-L1 expression: A pooled analysis of 3 randomized controlled trials. Cancer, 126(22), 4867–4877. https://doi.org/10.1002/cncr.33142

    Article  CAS  PubMed  Google Scholar 

  71. Robinson, A. G., Vicente, D., Tafreshi, A., Parra, H. S., Mazieres, J., Cicin, I., Medgyasszay, B., Rodríguez-Cid, J., Okamoto, I., Lee, S., Ramlau, R., Vladimirov, V., Cheng, Y., Halmos, B., Liu, C.-C., Schwarzenberger, P., Piperdi, B., & Paz-Ares, L. (2021). 97O first-line pembrolizumab plus chemotherapy for patients with advanced squamous NSCLC: 3-year follow-up from KEYNOTE-407. Journal of Thoracic Oncology, 16(4), S748–S749. https://doi.org/10.1016/S1556-0864(21)01939-0

    Article  Google Scholar 

  72. 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. (2018). Atezolizumab for first-Line treatment of metastatic nonsquamous NSCLC. The New England Journal of Medicine, 378(24), 2288–2301. https://doi.org/10.1056/NEJMoa1716948

    Article  CAS  PubMed  Google Scholar 

  73. 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. (2019). 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. The Lancet Respiratory Medicine, 7(5), 387–401. https://doi.org/10.1016/S2213-2600(19)30084-0

    Article  CAS  PubMed  Google Scholar 

  74. 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. (2019). 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. The Lancet Oncology, 20(7), 924–937. https://doi.org/10.1016/S1470-2045(19)30167-6

    Article  CAS  PubMed  Google Scholar 

  75. Jotte, R., Cappuzzo, F., Vynnychenko, I., Stroyakovskiy, D., Rodríguez-Abreu, D., Hussein, M., Soo, R., Conter, H. J., Kozuki, T., Huang, K.-C., Graupner, V., Sun, S. W., Hoang, T., Jessop, H., McCleland, M., Ballinger, M., Sandler, A., & Socinski, M. A. (2020). Atezolizumab in combination with carboplatin and nab-paclitaxel in advanced squamous NSCLC (IMpower131): Results from a randomized phase III trial. Journal of Thoracic Oncology, 15(8), 1351–1360. https://doi.org/10.1016/j.jtho.2020.03.028

    Article  CAS  PubMed  Google Scholar 

  76. Nishio, M., Barlesi, F., West, H., Ball, S., Bordoni, R., Cobo, M., Longeras, P. D., Goldschmidt, J., Jr., Novello, S., Orlandi, F., Sanborn, R. E., Szalai, Z., Ursol, G., Mendus, D., Wang, L., Wen, X., McCleland, M., Hoang, T., Phan, S., & Socinski, M. A. (2021). Atezolizumab plus chemotherapy for first-Line treatment of nonsquamous NSCLC: Results from the randomized phase 3 IMpower132 trial. Journal of Thoracic Oncology, 16(4), 653–664. https://doi.org/10.1016/j.jtho.2020.11.025

    Article  CAS  PubMed  Google Scholar 

  77. Hellmann, M. D., Paz-Ares, L., Bernabe Caro, R., Zurawski, B., Kim, S.-W., Carcereny Costa, E., Park, K., Alexandru, A., Lupinacci, L., de la Mora, J. E., Sakai, H., Albert, I., Vergnenegre, A., Peters, S., Syrigos, K., Barlesi, F., Reck, M., Borghaei, H., Brahmer, J. R., O’Byrne, K. J., Geese, W. J., Bhagavatheeswaran, P., Rabindran, S. K., Kasinathan, R. S., Nathan, F. E., & Ramalingam, S. S. (2019). Nivolumab plus Ipilimumab in advanced non-small-cell lung Cancer. The New England Journal of Medicine, 381(21), 2020–2031. https://doi.org/10.1056/NEJMoa1910231

    Article  CAS  PubMed  Google Scholar 

  78. Ramalingam, S. S., Ciuleanu, T. E., Pluzanski, A., Lee, J.-S., Schenker, M., Bernabe Caro, R., Lee, K. H., Zurawski, B., Audigier-Valette, C., Provencio, M., Linardou, H., Kim, S.-W., Borghaei, H., Hellmann, M. D., O’Byrne, K. J., Paz-Ares, L. G., Reck, M., Nathan, F. E., & Brahmer, J. R. (2020). Nivolumab + ipilimumab versus platinum-doublet chemotherapy as first-line treatment for advanced non-small cell lung cancer: Three-year update from CheckMate 227 Part 1. JCO, 38(15_suppl), 9500–9500. https://doi.org/10.1200/JCO.2020.38.15_suppl.9500

    Article  Google Scholar 

  79. Rizvi, N. A., Cho, B. C., Reinmuth, N., Lee, K. H., Luft, A., Ahn, M.-J., van den Heuvel, M. M., Cobo, M., Vicente, D., Smolin, A., Moiseyenko, V., Antonia, S. J., Le Moulec, S., Robinet, G., Natale, R., Schneider, J., Shepherd, F. A., Geater, S. L., Garon, E. B., Kim, E. S., Goldberg, S. B., Nakagawa, K., Raja, R., Higgs, B. W., Boothman, A.-M., Zhao, L., Scheuring, U., Stockman, P. K., Chand, V. K., & Peters, S. (2020). Durvalumab with or without Tremelimumab vs standard chemotherapy in first-line treatment of metastatic non-small cell lung Cancer: The MYSTIC phase 3 randomized clinical trial. JAMA Oncology, 6(5), 661–674. https://doi.org/10.1001/jamaoncol.2020.0237

    Article  PubMed  PubMed Central  Google Scholar 

  80. Si, H., Kuziora, M., Quinn, K. J., Helman, E., Ye, J., Liu, F., Scheuring, U., Peters, S., Rizvi, N. A., Brohawn, P. Z., Ranade, K., Higgs, B. W., Banks, K. C., Chand, V. K., & Raja, R. (2021). A blood-based assay for assessment of tumor mutational burden in first-line metastatic NSCLC treatment: Results from the MYSTIC study. Clinical Cancer Research, 27(6), 1631–1640. https://doi.org/10.1158/1078-0432.CCR-20-3771

    Article  CAS  PubMed  Google Scholar 

  81. Boyer, M., Şendur, M. A. N., Rodríguez-Abreu, D., Park, K., Lee, D. H., Çiçin, I., Yumuk, P. F., Orlandi, F. J., Leal, T. A., Molinier, O., Soparattanapaisarn, N., Langleben, A., Califano, R., Medgyasszay, B., Hsia, T.-C., Otterson, G. A., Xu, L., Piperdi, B., Samkari, A., & Reck, M. (2021). Pembrolizumab plus Ipilimumab or placebo for metastatic non-small-cell lung Cancer with PD-L1 tumor proportion score ≥ 50%: Randomized, double-blind phase III KEYNOTE-598 study. Journal of Clinical Oncology, JCO2003579. https://doi.org/10.1200/JCO.20.03579

  82. Paz-Ares, L., Ciuleanu, T.-E., Cobo, M., Schenker, M., Zurawski, B., Menezes, J., Richardet, E., Bennouna, J., Felip, E., Juan-Vidal, O., Alexandru, A., Sakai, H., Lingua, A., Salman, P., Souquet, P.-J., De Marchi, P., Martin, C., Pérol, M., Scherpereel, A., Lu, S., John, T., Carbone, D. P., Meadows-Shropshire, S., Agrawal, S., Oukessou, A., Yan, J., & Reck, M. (2021). First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): An international, randomised, open-label, phase 3 trial. The Lancet Oncology, 22(2), 198–211. https://doi.org/10.1016/S1470-2045(20)30641-0

    Article  CAS  PubMed  Google Scholar 

  83. Paz-Ares, L., Ciuleanu, T.-E., Cobo, M., Schenker, M., Zurawski, B., Menezes, J., Richardet, E., Bennouna, J., Felip, E., Juan-Vidal, O., Alexandru, A., Sakai, H., Scherpereel, A., Reck, M., Lu, S., John, T., Meadows-Shropshire, S., Balli, D., Agrawal, S., & Carbone, D. P. (2021). 98O first-line nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles chemotherapy (chemo) vs 4 cycles chemo in advanced non-small cell lung cancer (aNSCLC): Association of blood and tissue tumor mutational burden (TMB) with efficacy in CheckMate 9LA. Journal of Thoracic Oncology, 16(4), S750–S751. https://doi.org/10.1016/S1556-0864(21)01940-7

    Article  Google Scholar 

  84. Bernhardt, E. B., & Jalal, S. I. (2016). Small Cell Lung Cancer. Cancer Treatment and Research, 170, 301–322. https://doi.org/10.1007/978-3-319-40389-2_14

    Article  PubMed  Google Scholar 

  85. Denninghoff, V., Russo, A., de Miguel-Pérez, D., Malapelle, U., Benyounes, A., Gittens, A., Cardona, A. F., & Rolfo, C. (2021). Small cell lung Cancer: State of the art of the molecular and genetic landscape and novel perspective. Cancers, 13(7). https://doi.org/10.3390/cancers13071723

  86. Rudin, C. M., Brambilla, E., Faivre-Finn, C., & Sage, J. (2021). Small-cell lung cancer. Nature Reviews. Disease Primers, 7(1), 3. https://doi.org/10.1038/s41572-020-00235-0

    Article  PubMed  PubMed Central  Google Scholar 

  87. Armstrong, S. A., & Liu, S. V. (2020). Dashing decades of defeat: Long anticipated advances in the first-line treatment of extensive-stage small cell lung Cancer. Current Oncology Reports, 22(2), 20. https://doi.org/10.1007/s11912-020-0887-y

    Article  PubMed  Google Scholar 

  88. Schultheis, A. M., Scheel, A. H., Ozretić, L., George, J., Thomas, R. K., Hagemann, T., Zander, T., Wolf, J., & Buettner, R. (2015). PD-L1 expression in small cell neuroendocrine carcinomas. European Journal of Cancer, 51(3), 421–426. https://doi.org/10.1016/j.ejca.2014.12.006

    Article  CAS  PubMed  Google Scholar 

  89. Iams, W. T., Shiuan, E., Meador, C. B., Roth, M., Bordeaux, J., Vaupel, C., Boyd, K. L., Summitt, I. B., Wang, L. L., Schneider, J. T., Warner, J. L., Zhao, Z., & Lovly, C. M. (2019). Improved prognosis and increased tumor-infiltrating lymphocytes in patients who have SCLC with neurologic paraneoplastic syndromes. Journal of Thoracic Oncology, 14(11), 1970–1981. https://doi.org/10.1016/j.jtho.2019.05.042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Bonanno, L., Pavan, A., Dieci, M. V., Di Liso, E., Schiavon, M., Comacchio, G., Attili, I., Pasello, G., Calabrese, F., Rea, F., Favaretto, A., Rugge, M., Guarneri, V., Fassan, M., & Conte, P. F. (2018). The role of immune microenvironment in small-cell lung cancer: Distribution of PD-L1 expression and prognostic role of FOXP3-positive tumour infiltrating lymphocytes. European Journal of Cancer, 101, 191–200. https://doi.org/10.1016/j.ejca.2018.06.023

    Article  CAS  PubMed  Google Scholar 

  91. Berghoff, A. S., Ricken, G., Wilhelm, D., Rajky, O., Widhalm, G., Dieckmann, K., Birner, P., Bartsch, R., & Preusser, M. (2016). Tumor infiltrating lymphocytes and PD-L1 expression in brain metastases of small cell lung cancer (SCLC). Journal of Neuro-Oncology, 130(1), 19–29. https://doi.org/10.1007/s11060-016-2216-8

    Article  CAS  PubMed  Google Scholar 

  92. Reck, M., Bondarenko, I., Luft, A., Serwatowski, P., Barlesi, F., Chacko, R., Sebastian, M., Lu, H., Cuillerot, J.-M., & Lynch, T. J. (2013). Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: Results from a randomized, double-blind, multicenter phase 2 trial. Annals of Oncology, 24(1), 75–83. https://doi.org/10.1093/annonc/mds213

    Article  CAS  PubMed  Google Scholar 

  93. Reck, M., Luft, A., Szczesna, A., Havel, L., Kim, S.-W., Akerley, W., Pietanza, M. C., Wu, Y.-L., Zielinski, C., Thomas, M., Felip, E., Gold, K., Horn, L., Aerts, J., Nakagawa, K., Lorigan, P., Pieters, A., Kong Sanchez, T., Fairchild, J., & Spigel, D. (2016). Phase III randomized trial of Ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung Cancer. Journal of Clinical Oncology, 34(31), 3740–3748. https://doi.org/10.1200/JCO.2016.67.6601

    Article  CAS  PubMed  Google Scholar 

  94. Horn, L., Mansfield, A. S., Szczęsna, A., Havel, L., Krzakowski, M., Hochmair, M. J., Huemer, F., Losonczy, G., Johnson, M. L., Nishio, M., Reck, M., Mok, T., Lam, S., Shames, D. S., Liu, J., Ding, B., Lopez-Chavez, A., Kabbinavar, F., Lin, W., Sandler, A., & Liu, S. V. (2018). First-Line Atezolizumab plus chemotherapy in extensive-stage small-cell lung Cancer. The New England Journal of Medicine, 379(23), 2220–2229. https://doi.org/10.1056/NEJMoa1809064

    Article  CAS  PubMed  Google Scholar 

  95. Liu, S. V., Reck, M., Mansfield, A. S., Mok, T., Scherpereel, A., Reinmuth, N., Garassino, M. C., De Castro, C. J., Califano, R., Nishio, M., Orlandi, F., Alatorre-Alexander, J., Leal, T., Cheng, Y., Lee, J.-S., Lam, S., McCleland, M., Deng, Y., Phan, S., & Horn, L. (2021). Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung Cancer treated with Atezolizumab, carboplatin, and etoposide (IMpower133). Journal of Clinical Oncology, 39(6), 619–630. https://doi.org/10.1200/JCO.20.01055

    Article  PubMed  Google Scholar 

  96. Paz-Ares, L., Dvorkin, M., Chen, Y., Reinmuth, N., Hotta, K., Trukhin, D., Statsenko, G., Hochmair, M. J., Özgüroğlu, M., Ji, J. H., Voitko, O., Poltoratskiy, A., Ponce, S., Verderame, F., Havel, L., Bondarenko, I., Kazarnowicz, A., Losonczy, G., Conev, N. V., Armstrong, J., Byrne, N., Shire, N., Jiang, H., & Goldman, J. W. (2019). Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): A randomised, controlled, open-label, phase 3 trial. Lancet, 394(10212), 1929–1939. https://doi.org/10.1016/S0140-6736(19)32222-6

    Article  CAS  PubMed  Google Scholar 

  97. Goldman, J. W., Dvorkin, M., Chen, Y., Reinmuth, N., Hotta, K., Trukhin, D., Statsenko, G., Hochmair, M. J., Özgüroğlu, M., Ji, J. H., Garassino, M. C., Voitko, O., Poltoratskiy, A., Ponce, S., Verderame, F., Havel, L., Bondarenko, I., Każarnowicz, A., Losonczy, G., Conev, N. V., Armstrong, J., Byrne, N., Thiyagarajah, P., Jiang, H., & Paz-Ares, L. (2021). Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): Updated results from a randomised, controlled, open-label, phase 3 trial. The Lancet Oncology, 22(1), 51–65. https://doi.org/10.1016/S1470-2045(20)30539-8

    Article  CAS  PubMed  Google Scholar 

  98. Rudin, C. M., Awad, M. M., Navarro, A., Gottfried, M., Peters, S., Csőszi, T., Cheema, P. K., Rodriguez-Abreu, D., Wollner, M., Yang, J. C.-H., Mazieres, J., Orlandi, F. J., Luft, A., Gümüş, M., Kato, T., Kalemkerian, G. P., Luo, Y., Ebiana, V., Pietanza, M. C., & Kim, H. R. (2020). Pembrolizumab or placebo plus etoposide and platinum as first-Line therapy for extensive-stage small-cell lung Cancer: Randomized, double-blind, phase III KEYNOTE-604 study. Journal of Clinical Oncology, 38(21), 2369–2379. https://doi.org/10.1200/JCO.20.00793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Ready, N., Farago, A. F., de Braud, F., Atmaca, A., Hellmann, M. D., Schneider, J. G., Spigel, D. R., Moreno, V., Chau, I., Hann, C. L., Eder, J. P., Steele, N. L., Pieters, A., Fairchild, J., & Antonia, S. J. (2019). Third-Line Nivolumab monotherapy in recurrent SCLC: CheckMate 032. Journal of Thoracic Oncology, 14(2), 237–244. https://doi.org/10.1016/j.jtho.2018.10.003

    Article  CAS  PubMed  Google Scholar 

  100. Ready, N. E., Ott, P. A., Hellmann, M. D., Zugazagoitia, J., Hann, C. L., de Braud, F., Antonia, S. J., Ascierto, P. A., Moreno, V., Atmaca, A., Salvagni, S., Taylor, M., Amin, A., Camidge, D. R., Horn, L., Calvo, E., Li, A., Lin, W. H., Callahan, M. K., & Spigel, D. R. (2020). Nivolumab monotherapy and Nivolumab plus Ipilimumab in recurrent small cell lung Cancer: Results from the CheckMate 032 randomized cohort. Journal of Thoracic Oncology, 15(3), 426–435. https://doi.org/10.1016/j.jtho.2019.10.004

    Article  CAS  PubMed  Google Scholar 

  101. Spigel, D. R., Vicente, D., Ciuleanu, T. E., Gettinger, S., Peters, S., Horn, L., Audigier-Valette, C., Pardo Aranda, N., Juan-Vidal, O., Cheng, Y., Zhang, H., Shi, M., Luft, A., Wolf, J., Antonia, S., Nakagawa, K., Fairchild, J., Baudelet, C., Pandya, D., Doshi, P., Chang, H., & Reck, M. (2021). Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331(☆). Annals of Oncology. https://doi.org/10.1016/j.annonc.2021.01.071

  102. Ott, P. A., Elez, E., Hiret, S., Kim, D.-W., Morosky, A., Saraf, S., Piperdi, B., & Mehnert, J. M. (2017). Pembrolizumab in patients with extensive-stage small-cell lung Cancer: Results from the phase Ib KEYNOTE-028 study. Journal of Clinical Oncology, 35(34), 3823–3829. https://doi.org/10.1200/JCO.2017.72.5069

    Article  CAS  PubMed  Google Scholar 

  103. Chung, H. C., Lopez-Martin, J. A., Kao, S. C.-H., Miller, W. H., Ros, W., Gao, B., Marabelle, A., Gottfried, M., Zer, A., Delord, J.-P., Penel, N., Jalal, S. I., Xu, L., Zeigenfuss, S., Pruitt, S. K., & Piha-Paul, S. A. (2018). Phase 2 study of pembrolizumab in advanced small-cell lung cancer (SCLC): KEYNOTE-158. JCO, 36(15_suppl), 8506–8506. https://doi.org/10.1200/JCO.2018.36.15_suppl.8506

    Article  Google Scholar 

  104. Chung, H. C., Piha-Paul, S. A., Lopez-Martin, J., Schellens, J. H. M., Kao, S., Miller, W. H. J., Delord, J.-P., Gao, B., Planchard, D., Gottfried, M., Zer, A., Jalal, S. I., Penel, N., Mehnert, J. M., Matos, I., Bennouna, J., Kim, D.-W., Xu, L., Krishnan, S., Norwood, K., & Ott, P. A. (2020). Pembrolizumab after two or more lines of previous therapy in patients with recurrent or metastatic SCLC: Results from the KEYNOTE-028 and KEYNOTE-158 studies. Journal of Thoracic Oncology, 15(4), 618–627. https://doi.org/10.1016/j.jtho.2019.12.109

    Article  CAS  PubMed  Google Scholar 

  105. Pujol, J.-L., Greillier, L., Audigier-Valette, C., Moro-Sibilot, D., Uwer, L., Hureaux, J., Guisier, F., Carmier, D., Madelaine, J., Otto, J., Gounant, V., Merle, P., Mourlanette, P., Molinier, O., Renault, A., Rabeau, A., Antoine, M., Denis, M. G., Bommart, S., Langlais, A., Morin, F., & Souquet, P.-J. (2019). A randomized non-comparative phase II study of anti-programmed cell death-ligand 1 Atezolizumab or chemotherapy as second-Line therapy in patients with small cell lung Cancer: Results from the IFCT-1603 trial. Journal of Thoracic Oncology, 14(5), 903–913. https://doi.org/10.1016/j.jtho.2019.01.008

    Article  CAS  PubMed  Google Scholar 

  106. 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. (2020). First-line pembrolizumab in advanced non-small cell lung cancer patients with poor performance status. European Journal of Cancer, 130, 155–167. https://doi.org/10.1016/j.ejca.2020.02.023

    Article  CAS  PubMed  Google Scholar 

  107. Hajjar, J. (2019). Cancer immunotherapy for the immunosuppressed: Dissecting the conundrum of safety and efficacy. Journal of Immunotherapy and Precision Oncology, 2(3), 53–54. https://doi.org/10.4103/JIPO.JIPO_15_19

    Article  Google Scholar 

  108. Uldrick, T. S., Gonçalves, P. H., Abdul-Hay, M., Claeys, A. J., Emu, B., Ernstoff, M. S., Fling, S. P., Fong, L., Kaiser, J. C., Lacroix, A. M., Lee, S. Y., Lundgren, L. M., Lurain, K., Parsons, C. H., Peeramsetti, S., Ramaswami, R., Sharon, E., Sznol, M., Wang, C.-C. J., Yarchoan, R., & Cheever, M. A. (2019). Assessment of the safety of Pembrolizumab in patients with HIV and advanced Cancer-a phase 1 study. JAMA Oncology, 5(9), 1332–1339. https://doi.org/10.1001/jamaoncol.2019.2244

    Article  PubMed  PubMed Central  Google Scholar 

  109. Scilla, K. A., Russo, A., & Rolfo, C. (2019). Immunotherapy use in patients with HIV and non-small-cell lung Cancer: Current data. Journal of Immunotherapy and Precision Oncology, 2(3), 55–58. https://doi.org/10.4103/JIPO.JIPO_13_19

    Article  Google Scholar 

  110. Cortellini, A., Buti, S., Santini, D., Perrone, F., Giusti, R., Tiseo, M., Bersanelli, M., Michiara, M., Grassadonia, A., Brocco, D., Tinari, N., De Tursi, M., Zoratto, F., Veltri, E., Marconcini, R., Malorgio, F., Garufi, C., Russano, M., Anesi, C., Zeppola, T., Filetti, M., Marchetti, P., Botticelli, A., Antonini Cappellini, G. C., De Galitiis, F., Vitale, M. G., Sabbatini, R., Bracarda, S., Berardi, R., Rinaldi, S., Tudini, M., Silva, R. R., Pireddu, A., Atzori, F., Chiari, R., Ricciuti, B., Iacono, D., Migliorino, M. R., Rossi, A., Porzio, G., Cannita, K., Ciciarelli, V., Fargnoli, M. C., Ascierto, P. A., & Ficorella, C. (2019). Clinical outcomes of patients with advanced Cancer and pre-existing autoimmune diseases treated with anti-programmed Death-1 immunotherapy: A real-world transverse study. The Oncologist, 24(6), e327–e337. https://doi.org/10.1634/theoncologist.2018-0618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Leonardi, G. C., Gainor, J. F., Altan, M., Kravets, S., Dahlberg, S. E., Gedmintas, L., Azimi, R., Rizvi, H., Riess, J. W., Hellmann, M. D., & Awad, M. M. (2018). Safety of programmed Death-1 pathway inhibitors among patients with non-small-cell lung Cancer and preexisting autoimmune disorders. Journal of Clinical Oncology, 36(19), 1905–1912. https://doi.org/10.1200/JCO.2017.77.0305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Naing, A., Hajjar, J., Gulley, J. L., Atkins, M. B., Ciliberto, G., Meric-Bernstam, F., & Hwu, P. (2020). Strategies for improving the management of immune-related adverse events. Journal for Immunotherapy of Cancer, 8(2). https://doi.org/10.1136/jitc-2020-001754

  113. Smedman, T. M., Line, P.-D., Guren, T. K., & Dueland, S. (2018). Graft rejection after immune checkpoint inhibitor therapy in solid organ transplant recipients. Acta Oncologica, 57(10), 1414–1418. https://doi.org/10.1080/0284186X.2018.1479069

    Article  PubMed  Google Scholar 

  114. Fisher, J., Zeitouni, N., Fan, W., & Samie, F. H. (2020). Immune checkpoint inhibitor therapy in solid organ transplant recipients: A patient-centered systematic review. Journal of the American Academy of Dermatology, 82(6), 1490–1500. https://doi.org/10.1016/j.jaad.2019.07.005

    Article  CAS  PubMed  Google Scholar 

  115. Barlesi, F., Audigier-Valette, C., Felip, E., Ciuleanu, T.-E., Jao, K., Rijavec, E., Urban, L., Aucoin, J.-S., Zannori, C., Vermaelen, K., Frontera, O. A., Ready, N., Curioni, A., Linardou, H., Poddubskaya, E., Fischer, J. R., Pillai, R., Li, S., Acevedo, A., & Paz-Ares, L. (2019). Nivolumab plus low-dose IPILIMUMAB as first-Line treatment of advanced NSCLC: Overall survival analysis of Checkmate 817. Annals of Oncology, 30, xi33–xi34. https://doi.org/10.1093/annonc/mdz451.001

    Article  Google Scholar 

  116. Ardizzoni, A., Azevedo, S., Rubio Viquiera, B., Rodriguez Abreu, D., Alatorre-Alexander, J., Smit, H. J., Yu, J., Syrigos, K., Patel, H., Tolson, J., Cardona, A., Perez Moreno, P., & Newsom-Davis, T. (2019). LBA84 – primary results from TAIL, a global single-arm safety study of atezolizumab (atezo) monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer (NSCLC). Annals of Oncology, 30, v920–v921. https://doi.org/10.1093/annonc/mdz394.082

    Article  Google Scholar 

  117. Russo, A., Lopes, A. R., McCusker, M. G., Garrigues, S. G., Ricciardi, G. R., Arensmeyer, K. E., Scilla, K. A., Mehra, R., & Rolfo, C. (2020). New targets in lung Cancer (excluding EGFR, ALK, ROS1). Current Oncology Reports, 22(5), 48. https://doi.org/10.1007/s11912-020-00909-8

    Article  PubMed  Google Scholar 

  118. Gandara, D. R., Paul, S. M., Kowanetz, M., Schleifman, E., Zou, W., Li, Y., Rittmeyer, A., Fehrenbacher, L., Otto, G., Malboeuf, C., Lieber, D. S., Lipson, D., Silterra, J., Amler, L., Riehl, T., Cummings, C. A., Hegde, P. S., Sandler, A., Ballinger, M., Fabrizio, D., Mok, T., & Shames, D. S. (2018). Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nature Medicine, 24(9), 1441–1448. https://doi.org/10.1038/s41591-018-0134-3

    Article  CAS  PubMed  Google Scholar 

  119. Herbst, R. S., Lopes, G., Kowalski, D. M., Nishio, M., Wu, Y.-L., de Castro, J. G., Baas, P., Kim, D.-W., Gubens, M. A., Cristescu, R., Aurora-Garg, D., Albright, A., Ayers, M., Loboda, A., Lunceford, J., Kobie, J., Lubiniecki, G. M., Pietanza, M. C., Piperdi, B., & Mok, T. S. K. (2019). Association between tissue TMB (tTMB) and clinical outcomes with pembrolizumab monotherapy (pembro) in PD-L1-positive advanced NSCLC in the KEYNOTE-010 and -042 trials. Annals of Oncology, 30, v916–v917. https://doi.org/10.1093/annonc/mdz394.077

    Article  Google Scholar 

  120. Marabelle, A., Fakih, M., Lopez, J., Shah, M., Shapira-Frommer, R., Nakagawa, K., Chung, H. C., Kindler, H. L., Lopez-Martin, J. A., Miller, W. H. J., Italiano, A., Kao, S., Piha-Paul, S. A., Delord, J.-P., McWilliams, R. R., Fabrizio, D. A., Aurora-Garg, D., Xu, L., **, F., Norwood, K., & Bang, Y.-J. (2020). Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: Prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. The Lancet Oncology, 21(10), 1353–1365. https://doi.org/10.1016/S1470-2045(20)30445-9

    Article  CAS  PubMed  Google Scholar 

  121. Paz-Ares, L., Langer, C. J., Novello, S., Halmos, B., Cheng, Y., Gadgeel, S. M., Hui, R., Sugawara, S., Borghaei, H., Cristescu, R., Aurora-Garg, D., Albright, A., Loboda, A., Kobie, J., Lunceford, J., Ayers, M., Lubiniecki, G. M., Pietanza, M. C., Piperdi, B., & Garassino, M. C. (2019). LBA80 – Pembrolizumab (pembro) plus platinum-based chemotherapy (chemo) for metastatic NSCLC: Tissue TMB (tTMB) and outcomes in KEYNOTE-021, 189, and 407. Annals of Oncology, 30, v917–v918. https://doi.org/10.1093/annonc/mdz394.078

    Article  Google Scholar 

  122. Garassino, M. C., Gadgeel, S. M., Rodriguez-Abreu, D., Felip, E., Esteban, E., Speranza, G., Hochmair, M., Powell, S. F., Garon, E. B., Hui, R., Nogami, N., Cristescu, R., Morrissey, M., Loboda, A., Kobie, J., Ayers, M., Piperdi, B., Pietanza, M. C., Snyder, A., & Reck, M. (2020). Evaluation of blood TMB (bTMB) in KEYNOTE-189: Pembrolizumab (pembro) plus chemotherapy (chemo) with pemetrexed and platinum versus placebo plus chemo as first-line therapy for metastatic nonsquamous NSCLC. JCO, 38(15_suppl), 9521–9521. https://doi.org/10.1200/JCO.2020.38.15_suppl.9521

    Article  Google Scholar 

  123. Biton, J., Mansuet-Lupo, A., Pécuchet, N., Alifano, M., Ouakrim, H., Arrondeau, J., Boudou-Rouquette, P., Goldwasser, F., Leroy, K., Goc, J., Wislez, M., Germain, C., Laurent-Puig, P., Dieu-Nosjean, M.-C., Cremer, I., Herbst, R., Blons, H., & Damotte, D. (2018). TP53, STK11, and EGFR mutations predict tumor immune profile and the response to anti-PD-1 in lung adenocarcinoma. Clinical Cancer Research, 24(22), 5710–5723. https://doi.org/10.1158/1078-0432.CCR-18-0163

    Article  CAS  PubMed  Google Scholar 

  124. Skoulidis, F., Goldberg, M. E., Greenawalt, D. M., Hellmann, M. D., Awad, M. M., Gainor, J. F., Schrock, A. B., Hartmaier, R. J., Trabucco, S. E., Gay, L., Ali, S. M., Elvin, J. A., Singal, G., Ross, J. S., Fabrizio, D., Szabo, P. M., Chang, H., Sasson, A., Srinivasan, S., Kirov, S., Szustakowski, J., Vitazka, P., Edwards, R., Bufill, J. A., Sharma, N., Ou, S.-H. I., Peled, N., Spigel, D. R., Rizvi, H., Aguilar, E. J., Carter, B. W., Erasmus, J., Halpenny, D. F., Plodkowski, A. J., Long, N. M., Nishino, M., Denning, W. L., Galan-Cobo, A., Hamdi, H., Hirz, T., Tong, P., Wang, J., Rodriguez-Canales, J., Villalobos, P. A., Parra, E. R., Kalhor, N., Sholl, L. M., Sauter, J. L., Jungbluth, A. A., Mino-Kenudson, M., Azimi, R., Elamin, Y. Y., Zhang, J., Leonardi, G. C., Jiang, F., Wong, K.-K., Lee, J. J., Papadimitrakopoulou, V. A., Wistuba, I. I., Miller, V. A., Frampton, G. M., Wolchok, J. D., Shaw, A. T., Jänne, P. A., Stephens, P. J., Rudin, C. M., Geese, W. J., Albacker, L. A., & Heymach, J. V. (2018). STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discovery, 8(7), 822–835. https://doi.org/10.1158/2159-8290.CD-18-0099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Lamberti, G., Spurr, L. F., Li, Y., Ricciuti, B., Recondo, G., Umeton, R., Nishino, M., Sholl, L. M., Meyerson, M. L., Cherniack, A. D., & Awad, M. M. (2020). Clinicopathological and genomic correlates of programmed cell death ligand 1 (PD-L1) expression in nonsquamous non-small-cell lung cancer. Annals of Oncology, 31(6), 807–814. https://doi.org/10.1016/j.annonc.2020.02.017

    Article  CAS  PubMed  Google Scholar 

  126. Marinelli, D., Mazzotta, M., Scalera, S., Terrenato, I., Sperati, F., D’Ambrosio, L., Pallocca, M., Corleone, G., Krasniqi, E., Pizzuti, L., Barba, M., Carpano, S., Vici, P., Filetti, M., Giusti, R., Vecchione, A., Occhipinti, M., Gelibter, A., Botticelli, A., De Nicola, F., Ciuffreda, L., Goeman, F., Gallo, E., Visca, P., Pescarmona, E., Fanciulli, M., De Maria, R., Marchetti, P., Ciliberto, G., & Maugeri-Saccà, M. (2020). KEAP1-driven co-mutations in lung adenocarcinoma unresponsive to immunotherapy despite high tumor mutational burden. Annals of Oncology, 31(12), 1746–1754. https://doi.org/10.1016/j.annonc.2020.08.2105

    Article  CAS  PubMed  Google Scholar 

  127. Rizvi, N., Cho, B. C., Reinmuth, N., Lee, K. H., Luft, A., Ahn, M., Papadimitrakopoulou, V., Heymach, J., Scheuring, U., Higgs, B., Ye, J., Kuziora, M., Wu, S., Liu, F., Si, H., & Peters, S. (2019). OA04.07 mutations associated with sensitivity or resistance to immunotherapy in mNSCLC: Analysis from the MYSTIC trial. Journal of Thoracic Oncology, 14(10), S217. https://doi.org/10.1016/j.jtho.2019.08.428

    Article  Google Scholar 

  128. Krishnamurthy, N., Goodman, A. M., Barkauskas, D. A., & Kurzrock, R. (2021). STK11 alterations in the pan-cancer setting: Prognostic and therapeutic implications. European Journal of Cancer, 148, 215–229. https://doi.org/10.1016/j.ejca.2021.01.050

    Article  CAS  PubMed  Google Scholar 

  129. Skoulidis, F., Arbour, K., Hellmann, M., Patil, P., Marmarelis, M., Owen, D., Awad, M., Murray, J., Levy, B., Hellyer, J., Gainor, J., Stewart, T., Goldberg, S., Dimou, A., Bestvina, C., Cummings, A., Elamin, Y., Lam, V., Zhang, J., Shu, C., Riess, J., Blakely, C., Pecot, C., Mezquita, L., Tabbò, F., Sacher, A., Scheffler, M., Ricciuti, B., Venkatraman, D., Rizvi, H., Liu, C., Johnston, R., Ni, Y., Azok, J., Kier, M., Katz, S., Davies, K., Segal, J., Ritterhouse, L., Shaish, H., Lacroix, L., Memmott, R., Madrigal, J., Goldman, J., Lau, S., Killam, J., Walther, Z., Carter, B., Woodcock, M., Roth, J., Swisher, S., Leighl, N., Digumarthy, S., Mooradian, M., Rotow, J., Wolf, J., Scagliotti, G., Planchard, D., Besse, B., Bivona, T., Gandara, D., Garon, E., Rizvi, N., Camidge, D. R., Schalper, K., Herbst, R., Shaw, A., Neal, J., Wakelee, H., Brahmer, J., Jänne, P., Carbone, D., Aggarwal, C., Pennell, N., Rudin, C., Papadimitrakopoulou, V., & Heymach, J. (2019). MA11.11 STK11/LKB1 genomic alterations are associated with inferior clinical outcomes with chemo-immunotherapy in non-squamous NSCLC. Journal of Thoracic Oncology, 14(10), S294–S295. https://doi.org/10.1016/j.jtho.2019.08.591

    Article  Google Scholar 

  130. Gadgeel, S. M., Rodriguez-Abreu, D., Felip, E., Esteban, E., Speranza, G., Reck, M., Hui, R., Boyer, M., Garon, E. B., Horinouchi, H., Cristescu, R., Aurora-Garg, D., Loboda, A., Lunceford, J., Kobie, J., Ayers, M., Piperdi, B., Pietanza, M. C., & Garassino, M. C. (2020). Abstract LB-397: Pembrolizumab plus pemetrexed and platinum vs placebo plus pemetrexed and platinum as first-line therapy for metastatic nonsquamous NSCLC: Analysis of KEYNOTE-189 by STK11 and KEAP1 status. Cancer Research, 80(16 Supplement), LB-397. https://doi.org/10.1158/1538-7445.AM2020-LB-397

    Article  Google Scholar 

  131. Fujii, T., Naing, A., Rolfo, C., & Hajjar, J. (2018). Biomarkers of response to immune checkpoint blockade in cancer treatment. Critical Reviews in Oncology/Hematology, 130, 108–120. https://doi.org/10.1016/j.critrevonc.2018.07.010

    Article  PubMed  Google Scholar 

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Acknowledgement

Dr. Kaen reports clinical trial activities for Roche, Lilly Oncology, Clovis, MSD, AbbVie, Takeda, Novartis, Pfizer, Array BioPharma Inc., Servier, Nektar Therapeutics, Merck Healthcare KGaA, and GlaxoSmithKline and consultancy for Roche, Boehringer Ingelheim, Pfizer, MSD, BMS, Novartis, AstraZeneca, Raffo Tecnofarma, Varifarma, and Bayer. Dr. Minatta reports speaker bureau for Pfizer, Roche, and Takeda and advisory board role for LATAM MSD. Dr. Russo reports consultancy for AstraZeneca and MSD outside the submitted work. Dr. Malapelle has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientific, Eli Lilly, Diaceutics, GSK, Merck, and AstraZeneca, unrelated to the current work. Dr. Rolfo reports grants from MSD, AstraZeneca, Archer, Inivata, Merck Serono, and Mylan, nonfinancial support from Oncompass, grants from Lung Cancer Research Foundation-Pfizer, and nonfinancial support from Guardant Health and Biomark Inc. outside the submitted work. The other authors have no conflict of interests to declare.

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Authors and Affiliations

  1. Centro Oncologico Riojano (CORI), National University La Rioja, La Rioja, Argentina

    Diego L. Kaen

  2. Departament of Oncology, Hospital Italiano, Buenos Aires, Argentina

    Nicolas Minatta

  3. Medical Oncology Unit, A.O. Papardo, Messina, Italy

    Alessandro Russo

  4. Department of Public Health, University of Naples Federico II, Naples, Italy

    Umberto Malapelle

  5. Center for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai Medical System & Icahn School of Medicine, Mount Sinai, New York, NY, USA

    Diego de Miguel-Pérez & Christian Rolfo MD, PhD, MBA, Dr.h.c.

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  1. Diego L. Kaen
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  2. Nicolas Minatta
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  3. Alessandro Russo
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  4. Umberto Malapelle
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  5. Diego de Miguel-Pérez
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  6. Christian Rolfo MD, PhD, MBA, Dr.h.c.
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Correspondence to Christian Rolfo MD, PhD, MBA, Dr.h.c. .

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  1. Professor, Dept. of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Aung Naing

  2. Assistant Professor, Service Chief of Adult Allergy & Immunology, Division of Immunology, Allergy & Retrovirology Baylor College of Medicine and Texas Children’ Hospital, Houston, TX, USA

    Joud Hajjar

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Kaen, D.L., Minatta, N., Russo, A., Malapelle, U., de Miguel-Pérez, D., Rolfo, C. (2021). Immunotherapy in Lung Cancer: Are the Promises of Long-Term Benefit Finally Met?. In: Naing, A., Hajjar, J. (eds) Immunotherapy. Advances in Experimental Medicine and Biology, vol 1342. Springer, Cham. https://doi.org/10.1007/978-3-030-79308-1_4

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