Immune checkpoint inhibitors for non-small-cell lung cancer: Does that represent a ‘new frontier’?

Anti-Cancer Agents in Medicinal Chemistry

Volumn 15, Issue 3, 2015, Pages 307-313

  Pilotto, Sara ^a   Kinspergher, Stefania ^a   Peretti, Umberto ^a   Caliò, Anna ^b   Carbognin, Luisa ^a   Ferrara, Roberto ^a   Brunelli, Matteo ^b   Chilosi, Marco ^b   Tortora, Giampaolo ^a   Bria, Emilio ^a  

^a UNIVERSITY HOSPITAL OF VERONA   (Italy)

^b UNIVERSITY OF VERONA   (Italy)

Author keywords

Checkpoint inhibitors; CTLA 4; Immunotherapy; Ipilimumab; Nivolumab; Non small cell lung cancer; PD 1

Indexed keywords

ANTINEOPLASTIC AGENT; BELAGENPUMATUCEL L; BEVACIZUMAB; BMS 936559; CARBOPLATIN; CRIZOTINIB; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DOCETAXEL; ERLOTINIB; GEFITINIB; IMMUNE CHECKPOINT INHIBITOR; IPILIMUMAB; MELANOMA ANTIGEN 3; MPDL 3280A; NIVOLUMAB; PACLITAXEL; PEMBROLIZUMAB; PROGRAMMED DEATH 1 RECEPTOR; TECEMOTIDE; TICILIMUMAB; UNCLASSIFIED DRUG; IMMUNOSUPPRESSIVE AGENT;

ARTICLE; CANCER IMMUNOTHERAPY; DIARRHEA; DRUG DOSE ESCALATION; DRUG MEGADOSE; DRUG RESPONSE; GASTROINTESTINAL TOXICITY; HUMAN; IMMUNE RESPONSE; IMMUNIZATION; LOW DRUG DOSE; MELANOMA; NON SMALL CELL LUNG CANCER; NONHUMAN; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; PRURITUS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; SKIN TOXICITY; SMALL CELL LUNG CANCER; CARCINOMA, NON-SMALL-CELL LUNG; CHEMISTRY; IMMUNOTHERAPY; LUNG NEOPLASMS; PATHOLOGY;

ANTINEOPLASTIC AGENTS; CARCINOMA, NON-SMALL-CELL LUNG; HUMANS; IMMUNOSUPPRESSIVE AGENTS; IMMUNOTHERAPY; LUNG NEOPLASMS;

EID: 84930912300     PISSN: 18715206     EISSN: 18755992     Source Type: Journal    
DOI: 10.2174/1871520614666141110170259     Document Type: Article

References (43)

1. Strebhardt, K.; Ullrich, A. Paul Ehrlich's magic bullet concept: 100 years of progress. Nat. Rev. Cancer, 2008, 8(6), 473-870.
2. Druker, B. J.; Tamura, S.; Buchdunger, E.; Ohno, S.; Segal, G. M.; Fanning, S.; Zimmermann, J.; Lydon, N. B. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med., 1996, 2(5), 561-566.
3. McNutt, M. Cancer immunotherapy. Science, 2013, 342(6165), 1417.
4. Chen, D. S.; Mellman, I. Oncology meets immunology: The cancerimmunity cycle. Immunity, 2013, 39(1), 1-10.
5. Rosenberg, S. A. Progress in the development of immunotherapy for the treatment of patients with cancer. J. Int. Med., 2001, 250(6), 462-475.
6. Hodi, F. S.; O'Day, S. J.; McDermott, D. F.; Weber, R. W.; Sosman, J. A.; Haanen, J. B.; Gonzalez, R.; Robert, C.; Schadendorf, D.; Hassel, J. C.; Akerley, W.; Van den Eertwegh, A. J.; Lutzky, J.; Lorigan, P.; Vaubel, J. M.; Linette, G. P.; Hogg, D.; Ottensmeier, C. H.; Lebbe, C.; Peschel, C.; Quirt, I.; Clark, J. I.; Wolchok, J. D.; Weber, J. S.; Tian, J.; Yellin, M. J.; Nichol, G. M.; Hoos, A.; Urba, W. J. Improved survival with ipilimumab in patients with metastatic melanoma. New Eng. J. Med., 2010, 363(8), 711-723.
7. Kantoff, P. W.; Higano, C. S.; Shore, N. D.; Berger, E. R.; Small, E. J.; Penson, D. F.; Redfern, C. H.; Ferrari, A. C.; Dreicer, R.; Sims, R. B.; Xu, Y.; Frohlich, M. W.; Schellhammer, P. F.; Investigators, I. S. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New Eng. J. Med., 2010, 363(5), 411-422.
8. Paez, J. G.; Janne, P. A.; Lee, J. C.; Tracy, S.; Greulich, H.; Gabriel, S.; Herman, P.; Kaye, F. J.; Lindeman, N.; Boggon, T. J.; Naoki, K.; Sasaki, H.; Fujii, Y.; Eck, M. J.; Sellers, W. R.; Johnson, B. E.; Meyerson, M. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science, 2004, 304(5676), 1497-500.
9. Kwak, E. L.; Bang, Y. J.; Camidge, D. R.; Shaw, A. T.; Solomon, B.; Maki, R. G.; Ou, S. H.; Dezube, B. J.; Janne, P. A.; Costa, D. B.; Varella-Garcia, M.; Kim, W. H.; Lynch, T. J.; Fidias, P.; Stubbs, H.; Engelman, J. A.; Sequist, L. V.; Tan, W.; Gandhi, L.; Mino-Kenudson, M.; Wei, G. C.; Shreeve, S. M.; Ratain, M. J.; Settleman, J.; Christensen, J. G.; Haber, D. A.; Wilner, K.; Salgia, R.; Shapiro, G. I.; Clark, J. W.; Iafrate, A. J. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. New Engl. J. Med., 2010, 363(18), 1693-703.
10. Al-Shibli, K. I.; Donnem, T.; Al-Saad, S.; Persson, M.; Bremnes, R. M.; Busund, L. T. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin. Cancer Res., 2008, 14(16), 5220-5227.
11. Dieu-Nosjean, M. C.; Antoine, M.; Danel, C.; Heudes, D.; Wislez, M.; Poulot, V.; Rabbe, N.; Laurans, L.; Tartour, E.; De Chaisemartin, L.; Lebecque, S.; Fridman, W. H.; Cadranel, J. Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J. Clin. Oncology: Off. J. Am. Society Clin. Oncology, 2008, 26(27), 4410-4417.
12. Platonova, S.; Cherfils-Vicini, J.; Damotte, D.; Crozet, L.; Vieillard, V.; Validire, P.; Andre, P.; Dieu-Nosjean, M. C.; Alifano, M.; Regnard, J. F.; Fridman, W. H.; Sautes-Fridman, C.; Cremer, I. Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res., 2011, 71(16), 5412-5422.
13. Imielinski, M.; Berger, A. H.; Hammerman, P. S.; Hernandez, B.; Pugh, T. J.; Hodis, E.; Cho, J.; Suh, J.; Capelletti, M.; Sivachenko, A.; Sougnez, C.; Auclair, D.; Lawrence, M. S.; Stojanov, P.; Cibulskis, K.; Choi, K.; De Waal, L.; Sharifnia, T.; Brooks, A.; Greulich, H.; Banerji, S.; Zander, T.; Seidel, D.; Leenders, F.; Ansen, S.; Ludwig, C.; Engel-Riedel, W.; Stoelben, E.; Wolf, J.; Goparju, C.; Thompson, K.; Winckler, W.; Kwiatkowski, D.; Johnson, B. E.; Janne, P. A.; Miller, V. A.; Pao, W.; Travis, W. D.; Pass, H. I.; Gabriel, S. B.; Lander, E. S.; Thomas, R. K.; Garraway, L. A.; Getz, G.; Meyerson, M. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell, 2012, 150(6), 1107-1120.
14. Butts, C.; Maksymiuk, A.; Goss, G.; Soulieres, D.; Marshall, E.; Cormier, Y.; Ellis, P. M.; Price, A.; Sawhney, R.; Beier, F.; Falk, M.; Murray, N. Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): Phase IIB randomized, multicenter, open-label trial. J. Cancer Res. Clin. Oncol., 2011, 137(9), 1337-42.
15. DeGregorio, M.; Soe, L.; Wolf, M., Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small cell lung cancer (START): A randomized, double-blind, phase III trial. J. Thoracic. Dis., 2014, 6(6), 571-573.
16. Sienel, W.; Varwerk, C.; Linder, A.; Kaiser, D.; Teschner, M.; Delire, M.; Stamatis, G.; Passlick, B. Melanoma associated antigen (MAGE)-A3 expression in Stages I and II non-small cell lung cancer: Results of a multi-center study. Eur. J. Cardiothorac. Surg., 2004, 25(1), 131-134.
17. Vansteenkiste, J.; Zielinski, M.; Linder, A.; Dahabreh, J.; Gonzalez, E. E.; Malinowski, W.; Lopez-Brea, M.; Vanakesa, T.; Jassem, J.; Kalofonos, H.; Perdeus, J.; Bonnet, R.; Basko, J.; Janilionis, R.; Passlick, B.; Treasure, T.; Gillet, M.; Lehmann, F. F.; Brichard, V. G. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: Phase II randomized study results. J. Clin. Oncol., 2013, 31(19), 2396-2403.
18. Tyagi, P.; Mirakhur, B., MAGRIT: The largest-ever phase III lung cancer trial aims to establish a novel tumor-specific approach to therapy. Clin. Lung Cancer, 2009, 10(5), 371-374.
19. Nemunaitis, J.; Dillman, R. O.; Schwarzenberger, P. O.; Senzer, N.; Cunningham, C.; Cutler, J.; Tong, A.; Kumar, P.; Pappen, B.; Hamilton, C.; DeVol, E.; Maples, P. B.; Liu, L.; Chamberlin, T.; Shawler, D. L.; Fakhrai, H. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J. Clin. Oncol., 2006, 24(29), 4721-4730.
20. Giaccone, G. In Belagenpumatucel-L therapeutic tumor cell vaccine for non-small cell lung cancer, European Cancer Congress, Amsterdam, Amsterdam, 2013.
21. Pardoll, D. M., The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer, 2012, 12(4), 252-264.
22. Chambers, C. A.; Kuhns, M. S.; Egen, J. G.; Allison, J. P. CTLA-4-mediated inhibition in regulation of T cell responses: Mechanisms and manipulation in tumor immunotherapy. Ann. Rev. Immunology, 2001, 19, 565-594.
23. Waterhouse, P.; Penninger, J. M.; Timms, E.; Wakeham, A.; Shahinian, A.; Lee, K. P.; Thompson, C. B.; Griesser, H.; Mak, T. W. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science, 1995, 270(5238), 985-988.
24. Salvi, S.; Fontana, V.; Boccardo, S.; Merlo, D. F.; Margallo, E.; Laurent, S.; Morabito, A.; Rijavec, E.; Dal Bello, M. G.; Mora, M.; Ratto, G. B.; Grossi, F.; Truini, M.; Pistillo, M. P. Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer. Cancer Immunol. Immunother., CII 2012, 61(9), 1463-1472.
25. Lynch, T. J.; Bondarenko, I.; Luft, A.; Serwatowski, P.; Barlesi, F.; Chacko, R.; Sebastian, M.; Neal, J.; Lu, H.; Cuillerot, J. M.; Reck, M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: Results from a randomized, double-blind, multicenter phase II study. J. Clin. Oncol., 2012, 30(17), 2046-2054.
26. Reck, M.; Bondarenko, I.; Luft, A.; Serwatowski, P.; Barlesi, F.; Chacko, R.; Sebastian, M.; Lu, H.; Cuillerot, J. M.; Lynch, T. J. Ipilimumab in combination with paclitaxel and carboplatin as firstline therapy in extensive-disease-small-cell lung cancer: Results from a randomized, double-blind, multicenter phase 2 trial. Ann. Oncology: Off. J. Eur. Society for Med. Oncology/ESMO, 2013, 24(1), 75-83.
27. Ribas, A.; Kefford, R.; Marshall, M. A.; Punt, C. J.; Haanen, J. B.; Marmol, M.; Garbe, C.; Gogas, H.; Schachter, J.; Linette, G.; Lorigan, P.; Kendra, K. L.; Maio, M.; Trefzer, U.; Smylie, M.; McArthur, G. A.; Dreno, B.; Nathan, P. D.; Mackiewicz, J.; Kirkwood, J. M.; Gomez-Navarro, J.; Huang, B.; Pavlov, D.; Hauschild, A. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J. Clin. Oncol., 2013, 31(5), 616-622.
28. Zatloukal, P.; Heo, D. S.; Park, K.; Kang, J.; Butts, C.; Bradford, D.; Graziano, S.; Huang, B.; Healey, D. Randomized phase II clinical trial comparing tremelimumab (CP-675, 206) with best supportive care (BSC) following first-line platinum-based therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC). ASCO Meeting Abstracts, 2009, 27(15S), 8071.
29. Keir, M. E.; Butte, M. J.; Freeman, G. J.; Sharpe, A. H. PD-1 and its ligands in tolerance and immunity. Ann. Rev. Immunol., 2008, 26, 677-704.
30. Ahmadzadeh, M.; Johnson, L. A.; Heemskerk, B.; Wunderlich, J. R.; Dudley, M. E.; White, D. E.; Rosenberg, S. A. Tumor antigenspecific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood, 2009, 114(8), 1537-1544.
31. 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. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. The New Eng. J. Med., 2012, 366(26), 2443-2454.
32. Brahmer, J. R. In Clinical activity, safety and subpopulation response anlaysis of Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with non-small cell lung cancer (NSCLC) ELCC, 2014.
33. Hamid, O.; Robert, C.; Daud, A.; Hodi, F. S.; Hwu, W. J.; Kefford, R.; Wolchok, J. D.; Hersey, P.; Joseph, R. W.; Weber, J. S.; Dronca, R.; Gangadhar, T. C.; Patnaik, A.; Zarour, H.; Joshua, A. M.; Gergich, K.; Elassaiss-Schaap, J.; Algazi, A.; Mateus, C.; Boasberg, P.; Tumeh, P. C.; Chmielowski, B.; Ebbinghaus, S. W.; Li, X. N.; Kang, S. P.; Ribas, A. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. The New Engl. J. Med., 2013, 369(2), 134-144.
34. Rizvi, N. In Safety and clinical activity of Pembrolizumab (MK-3475) as initial therapy in patients with advanced non-small cell lung cancer (NSCLC), ASCO Annual Meeting, 2014.
35. Yang, C. Y.; Lin, M. W.; Chang, Y. L.; Wu, C. T.; Yang, P. C. Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes. Eur. J. Cancer, 2014, 50(7), 1361-1369.
36. Velcheti, V.; Schalper, K. A.; Carvajal, D. E.; Anagnostou, V. K.; Syrigos, K. N.; Sznol, M.; Herbst, R. S.; Gettinger, S. N.; Chen, L.; Rimm, D. L. Programmed death ligand-1 expression in non-small cell lung cancer. Laboratory investigation: J. Tec. Methods pathol., 2014, 94(1), 107-116.
37. Mu, C. Y.; Huang, J. A.; Chen, Y.; Chen, C.; Zhang, X. G. High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med. Oncol., 2011, 28(3), 682-688.
38. Brahmer, J. R.; Tykodi, S. S.; Chow, L. Q.; 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. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. The New Engl. J. Med., 2012, 366(26), 2455-2465.
39. Soria, J. In Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC): Additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PD-L1), European Cancer Congress, 2013.
40. Sundar, R.; Soong, R.; Cho, B. C.; Brahmer, J. R.; Soo, R. A. Immunotherapy in the treatment of non-small cell lung cancer. Lung cancer, 2014.
41. Oxnard, G. R.; Morris, M. J.; Hodi, F. S.; Baker, L. H.; Kris, M. G.; Venook, A. P.; Schwartz, L. H. When progressive disease does not mean treatment failure: Reconsidering the criteria for progression. J. Nat. Cancer Institute, 2012, 104(20), 1534-1541.
42. Wolchok, J. D.; Hoos, A.; O'Day, S.; Weber, J. S.; Hamid, O.; Lebbe, C.; Maio, M.; Binder, M.; Bohnsack, O.; Nichol, G.; Humphrey, R.; Hodi, F. S. Guidelines for the evaluation of immune therapy activity in solid tumors: Immune-related response criteria. Clin. Cancer Research: An off. J. Am. Ass. Cancer Res., 2009, 15(23), 7412-7420.
43. Hamid, O.; Schmidt, H.; Nissan, A.; Ridolfi, L.; Aamdal, S.; Hansson, J.; Guida, M.; Hyams, D. M.; Gomez, H.; Bastholt, L.; Chasalow, S. D.; Berman, D. A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. J. Trans. Med., 2011, 9, 204.