Skip to main content
SpringerLink
Log in

The Role of Targeted Agents and Immunotherapy in Older Patients with Non-small Cell Lung Cancer

  • Review Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Lung cancer is predominantly a disease of the elderly. This subgroup of patients poses many challenges and an appropriate geriatric assessment is crucial for treatment personalisation in order to reduce the risk of over- or under-treatment. Whilst cytotoxic chemotherapy has been the backbone of advanced non-small cell lung cancer (NSCLC) treatment for decades, the development of targeted agents for driver mutations such as EGFR, ALK, BRAF and ROS1 has changed the treatment paradigm and natural history of this disease. More recently, the development of immune checkpoint inhibitors has revolutionised treatment for a larger group of patients with locally advanced/metastatic disease. Limited data exist on safety and efficacy of these agents in the elderly population. Many questions remain regarding the available evidence for targeted therapies and immune checkpoint blockade in NSCLC and, in particular, their role in this subgroup of patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Novello S, Barlesi F, Califano R, Cufer T, Ekman S, Levra MG, et al. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v1–27.

    Article  PubMed  CAS  Google Scholar 

  2. Royal College of Physicians. National Lung Cancer Audit annual report 2016 (for the audit period 2015). London: Royal College of Physicians; 2017.

    Google Scholar 

  3. National Cancer Institute—SEER Program. SEER Cancer Stat Facts: lung and bronchus cancer. 2017. https://seer.cancer.gov/statfacts/html/lungb.html. Accessed 05 Apr 2018.

  4. Extermann M, Aapro M, Bernabei R, Cohen HJ, Droz JP, Lichtman S, et al. Use of comprehensive geriatric assessment in older cancer patients: recommendations from the Task Force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol. 2005;55(3):241–52.

    Article  PubMed  Google Scholar 

  5. Pallis AG, Gridelli C, Wedding U, Faivre-Finn C, Veronesi G, Jaklitsch M, et al. Management of elderly patients with NSCLC; updated expert’s opinion paper: EORTC Elderly Task Force, Lung Cancer Group and International Society for Geriatric Oncology. Ann Oncol. 2014;25(7):1270–83.

    Article  PubMed  CAS  Google Scholar 

  6. Corre R, Greillier L, Le Caer H, Audigier-Valette C, Baize N, Berard H, et al. Use of a comprehensive geriatric assessment for the management of elderly patients with advanced non-small-cell lung cancer: the phase III RANDOMIZED ESOGIA-GFPC-GECP 08-02 study. J Clin Oncol. 2016;34(13):1476–83.

    Article  PubMed  CAS  Google Scholar 

  7. Le Caer H, Borget I, Corre R, Locher C, Raynaud C, Decroisette C, et al. Prognostic role of a comprehensive geriatric assessment on the management of elderly patients with advanced non-small cell lung cancer (NSCLC): a pooled analysis of two prospective phase II trials by the GFPC Group. J Thorac Dis. 2017;9(10):3747–54.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J, et al. Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer. 2012;118(13):3377–86.

    Article  PubMed  Google Scholar 

  9. Hurria A, Mohile S, Gajra A, Klepin H, Muss H, Chapman A, et al. Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. J Clin Oncol. 2016;34(20):2366–71.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Daste A, Chakiba C, Domblides C, Gross-Goupil M, Quivy A, Ravaud A, et al. Targeted therapy and elderly people: a review. Eur J Cancer. 2016;69:199–215.

    Article  PubMed  Google Scholar 

  12. Daste A, Domblides C, Gross-Goupil M, Chakiba C, Quivy A, Cochin V, et al. Immune checkpoint inhibitors and elderly people: a review. Eur J Cancer. 2017;82:155–66.

    Article  PubMed  CAS  Google Scholar 

  13. Talarico L, Chen G, Pazdur R. Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol. 2004;22(22):4626–31.

    Article  PubMed  Google Scholar 

  14. Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 2015;5(9):2892–911.

    PubMed  PubMed Central  Google Scholar 

  15. Chia PL, Mitchell P, Dobrovic A, John T. Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors. Clin Epidemiol. 2014;6:423–32.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Planchard D, Smit EF, Groen HJM, Mazieres J, Besse B, Helland Å, et al. Dabrafenib plus trametinib in patients with previously untreated BRAF V600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017;18(10):1307–16.

    Article  PubMed  CAS  Google Scholar 

  17. Luk PP, Yu B, Ng CC, Mercorella B, Selinger C, Lum T, et al. BRAF mutations in non-small cell lung cancer. Transl Lung Cancer Res. 2015;4(2):142–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  18. Goodgame B, Viswanathan A, Zoole J, Gao F, Miller CR, Subramanian J, et al. Risk of recurrence of resected stage I non-small cell lung cancer in elderly patients as compared with younger patients. J Thorac Oncol. 2009;4(11):1370–4.

    Article  PubMed  Google Scholar 

  19. Fumagalli C, Barberis M, Vacirca D, Lombardi F, Bagnardi V, Marinis FD, et al. Molecular profile in non-small cell lung cancers (NSCLCs) occurring in elderly. J Clin Oncol. 2016;34(15_suppl):10053.

    Article  Google Scholar 

  20. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12(8):735–42.

    Article  PubMed  CAS  Google Scholar 

  21. Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, et al. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015;26(9):1883–9.

    Article  PubMed  Google Scholar 

  22. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46.

    Article  PubMed  CAS  Google Scholar 

  23. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, West Japan Oncology Group, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11(2):121–8.

    Article  PubMed  CAS  Google Scholar 

  24. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. North–East Japan Study Group Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380–8.

    Article  PubMed  CAS  Google Scholar 

  25. Mok TS, Wu Y-L, Thongprasert S, Yang C-H, Chu D-T, Saijo N, et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–57.

    Article  PubMed  CAS  Google Scholar 

  26. Sequist LV, Yang JC-H, Yamamoto N, O’Byrne K, Hirsh V, Mok T, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327–34.

    Article  PubMed  CAS  Google Scholar 

  27. Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, et al. 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):213–22.

    Article  PubMed  CAS  Google Scholar 

  28. Soria J-C, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, FLAURA Investigators, et al. Osimertinib in untreated EGFR-mutated advanced non–small-cell lung cancer. N Engl J Med. 2018;378(2):113–25.

    Article  PubMed  Google Scholar 

  29. Inoue Y, Inui N, Asada K, Karayama M, Matsuda H, Yokomura K, et al. Phase II study of erlotinib in elderly patients with non-small cell lung cancer harboring epidermal growth factor receptor mutations. Cancer Chemother Pharmacol. 2015;76(1):155–61.

    Article  PubMed  CAS  Google Scholar 

  30. Jackman DM, Yeap BY, Lindeman NI, Fidias P, Rabin MS, Temel J, et al. Phase II clinical trial of chemotherapy-naive patients > or = 70 years of age treated with erlotinib for advanced non-small-cell lung cancer. J Clin Oncol. 2007;25(7):760–6.

    Article  PubMed  CAS  Google Scholar 

  31. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353(2):123–32.

    Article  PubMed  CAS  Google Scholar 

  32. Wheatley-Price P, Ding K, Seymour L, Clark GM, Shepherd FA. Erlotinib for advanced non-small-cell lung cancer in the elderly: an analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol. 2008;26(14):2350–7.

    Article  PubMed  CAS  Google Scholar 

  33. Brueckl WM, Achenbach HJ, Ficker JH, Schuette W. Erlotinib treatment after platinum-based therapy in elderly patients with non-small-cell lung cancer in routine clinical practice—results from the ElderTac study. BMC Cancer. 2018;18(1):333.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Inoue A, Kobayashi K, Usui K, Maemondo M, Okinaga S, Mikami I, et al. First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy. J Clin Oncol. 2009;27(9):1394–400.

    Article  PubMed  CAS  Google Scholar 

  35. Maemondo M, Minegishi Y, Inoue A, Kobayashi K, Harada M, Okinaga S, et al. First-line gefitinib in patients aged 75 or older with advanced non-small cell lung cancer harboring epidermal growth factor receptor mutations: NEJ 003 study. J Thorac Oncol. 2012;7(9):1417–22.

    Article  PubMed  CAS  Google Scholar 

  36. Kuwako T, Imai H, Masuda T, Miura Y, Seki K, Yoshino R, et al. First-line gefitinib treatment in elderly patients (aged >/=75 years) with non-small cell lung cancer harboring EGFR mutations. Cancer Chemother Pharmacol. 2015;76(4):761–9.

    Article  PubMed  CAS  Google Scholar 

  37. Park K, Tan EH, O’Byrne K, Zhang L, Boyer M, Mok T, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016;17(5):577–89.

    Article  PubMed  CAS  Google Scholar 

  38. Paz-Ares L, Tan EH, O’Byrne K, Zhang L, Hirsh V, Boyer M, et al. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial. Ann Oncol. 2017;28(2):270–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Wu Y-L, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(11):1454–66.

    Article  PubMed  CAS  Google Scholar 

  40. Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, et al. AURA3 Investigators. Osimertinib or platinum–pemetrexed in EGFR T790M–positive lung cancer. N Engl J Med. 2017;376(7):629–40.

    Article  PubMed  CAS  Google Scholar 

  41. Solomon BJ, Mok T, Kim D-W, Wu Y-L, Nakagawa K, Mekhail T, et al. PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in alk-positive lung cancer. N Engl J Med. 2014;371(23):2167–77.

    Article  PubMed  CAS  Google Scholar 

  42. Shaw AT, Kim D-W, Nakagawa K, Seto T, Crinó L, Ahn M-J, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385–94.

    Article  PubMed  CAS  Google Scholar 

  43. Soria JC, Tan DSW, Chiari R, Wu YL, Paz-Ares L, Wolf J, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389(10072):917–29.

    Article  PubMed  CAS  Google Scholar 

  44. Yang JC, Ou SI, De Petris L, Gadgeel S, Gandhi L, Kim DW, et al. Pooled systemic efficacy and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small cell lung cancer. J Thorac Oncol. 2017;12(10):1552–60.

    Article  PubMed  Google Scholar 

  45. Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim D-W, ALEX Trial Investigators, et al. Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer. N Engl J Med. 2017;377(9):829–38.

    Article  PubMed  CAS  Google Scholar 

  46. Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017;390(10089):29–39.

    Article  PubMed  CAS  Google Scholar 

  47. Kim DW, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, et al. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized, multicenter phase II trial. J Clin Oncol. 2017;35(22):2490–8.

    Article  PubMed  Google Scholar 

  48. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  PubMed  CAS  Google Scholar 

  49. Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329–60.

    Article  PubMed  CAS  Google Scholar 

  50. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480(7378):480–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Weber J. Immune checkpoint proteins: a new therapeutic paradigm for cancer–preclinical background: CTLA-4 and PD-1 blockade. Semin Oncol. 2010;37(5):430–9.

    Article  PubMed  CAS  Google Scholar 

  52. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW. Cancer genome landscapes. Science. 2013;339(6127):1546–58.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499(7457):214–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, et al. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017;376(25):2415–26.

    Article  PubMed  CAS  Google Scholar 

  55. Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P, Halpenny D, et al. Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing. J Clin Oncol. 2018;36(7):633–41.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol. 2004;5(2):133–9.

    Article  PubMed  CAS  Google Scholar 

  57. Pang WW, Price EA, Sahoo D, Beerman I, Maloney WJ, Rossi DJ, et al. Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Proc Natl Acad Sci USA. 2011;108(50):20012–7.

    Article  PubMed  Google Scholar 

  58. Lin J, Zhu Z, Xiao H, Wakefield MR, Ding VA, Bai Q, et al. The role of IL-7 in Immunity and Cancer. Anticancer Res. 2017;37(3):963–7.

    Article  PubMed  Google Scholar 

  59. Metcalf TU, Cubas RA, Ghneim K, Cartwright MJ, Grevenynghe JV, Richner JM, et al. Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors. Aging Cell. 2015;14(3):421–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Manser AR, Uhrberg M. Age-related changes in natural killer cell repertoires: impact on NK cell function and immune surveillance. Cancer Immunol Immunother. 2016;65(4):417–26.

    Article  PubMed  CAS  Google Scholar 

  61. Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nat Rev Immunol. 2013;13(12):875–87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Goronzy JJ, Fang F, Cavanagh MM, Qi Q, Weyand CM. Naive T cell maintenance and function in human aging. J Immunol. 2015;194(9):4073–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Fagnoni FF, Vescovini R, Passeri G, Bologna G, Pedrazzoni M, Lavagetto G, et al. Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. Blood. 2000;95(9):2860–8.

    PubMed  CAS  Google Scholar 

  64. Dock JN, Effros RB. Role of CD8 T cell replicative senescence in human aging and in HIV-mediated immunosenescence. Aging Dis. 2011;2(5):382–97.

    PubMed  PubMed Central  Google Scholar 

  65. Farber DL, Yudanin NA, Restifo NP. Human memory T cells: generation, compartmentalization and homeostasis. Nat Rev Immunol. 2014;14(1):24–35.

    Article  PubMed  CAS  Google Scholar 

  66. Grolleau-Julius A, Harning EK, Abernathy LM, Yung RL. Impaired dendritic cell function in aging leads to defective antitumor immunity. Cancer Res. 2008;68(15):6341–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Plowden J, Renshaw-Hoelscher M, Gangappa S, Engleman C, Katz JM, Sambhara S. Impaired antigen-induced CD8+ T cell clonal expansion in aging is due to defects in antigen presenting cell function. Cell Immunol. 2004;229(2):86–92.

    Article  PubMed  CAS  Google Scholar 

  68. Sridharan A, Esposo M, Kaushal K, Tay J, Osann K, Agrawal S, et al. Age-associated impaired plasmacytoid dendritic cell functions lead to decreased CD4 and CD8 T cell immunity. Age. 2011;33(3):363–76.

    Article  PubMed  CAS  Google Scholar 

  69. Verschoor CP, Johnstone J, Millar J, Dorrington MG, Habibagahi M, Lelic A, et al. Blood CD33(+)HLA-DR(−) myeloid-derived suppressor cells are increased with age and a history of cancer. J Leukoc Biol. 2013;93(4):633–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Pawelec G. Immunosenescence and cancer. Biogerontology. 2017;18(4):717–21.

    Article  PubMed  CAS  Google Scholar 

  71. Lages CS, Suffia I, Velilla PA, Huang B, Warshaw G, Hildeman DA, et al. Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation. J Immunol. 2008;181(3):1835–48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Herbst RS, Baas P, Kim D-W, Felip E, Pérez-Gracia JL, Han J-Y, et al. 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):1540–50.

    Article  PubMed  CAS  Google Scholar 

  73. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–33.

    Article  PubMed  CAS  Google Scholar 

  74. Brahmer J, Rodríguez-Abreu D, Robinson A, Hui R, Csőszi T, Fülöp A, et al. Updated analysis of KEYNOTE-024: pembrolizumab vs platinum-based chemotherapy for advanced NSCLC with PD-L1 TPS ≥50%. J Thorac Oncol. 2017;12(11):S1793–4 (abstract no. OA 17.06).

    Article  Google Scholar 

  75. Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017;18(12):1600–9.

    Article  PubMed  CAS  Google Scholar 

  76. Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497–508.

    Article  PubMed  CAS  Google Scholar 

  77. Borghaei H, Langer CJ, Gadgeel S, Papadimitrakopoulou VA, Patnaik A, Powell SF, et al. Updated results from KEYNOTE-021 cohort G: a randomized, phase 2 study of pemetrexed and carboplatin (PC) with or without pembrolizumab (pembro) as first-line therapy for advanced nonsquamous NSCLC. Ann Oncol. 2017;28(suppl_5):636–7 (abstract no. LBA49).

    Article  Google Scholar 

  78. Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078–92.

    Article  PubMed  CAS  Google Scholar 

  79. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WEE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Reck M, Taylor F, Penrod JR, DeRosa M, Morrissey L, Dastani H, et al. Impact of nivolumab versus docetaxel on health-related quality of life and symptoms in patients with advanced squamous non-small cell lung cancer: results from the CheckMate 017 Study. J Thorac Oncol. 2018;13(2):194–204.

    Article  PubMed  Google Scholar 

  81. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, et al. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017;35(35):3924–33.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Singh H, Kim G, Maher VE, Beaver JA, Pai-Scherf LH, Balasubramaniam S, et al. FDA subset analysis of the safety of nivolumab in elderly patients with advanced cancers. J Clin Oncol. 2016;34(15_suppl):10010 (abstract).

    Article  Google Scholar 

  84. Popat S, Ardizzoni A, Ciuleanu T, Cobo Dols M, Laktionov K, Szilasi M, et al. Nivolumab in previously treated patients with metastatic squamous NSCLC: results of a European single-arm, phase 2 trial (CheckMate 171) including patients aged ≥70 years and with poor performance status. Ann Oncol. 2017;28(suppl_5):463 (abstract no. 1303PD).

    Article  Google Scholar 

  85. Grossi F, Crinò L, Misino A, Bidoli P, Delmonte A, Gelsomino F, et al. Efficacy and safety of nivolumab in elderly patients (pts) with advanced squamous non small cell lung cancer (Sq-NSCLC) participating in the expanded access programme (EAP) in Italy. Ann Oncol. 2016;27(suppl_6):1079 (abstract).

    Article  Google Scholar 

  86. Migliorino MR, Gelibter A, Grossi F, Fagnani D, Bordi P, Franchina T, et al. Use of nivolumab in elderly patients with advanced non-squamous NSCLC: results from the Italian expanded access program (EAP). Ann Oncol. 2017;28(suppl_5):471 (abstract no. 1320P).

    Article  Google Scholar 

  87. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255–65.

    Article  PubMed  Google Scholar 

  88. Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, POPLAR Study Group, et al. 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):1837–46.

    Article  PubMed  CAS  Google Scholar 

  89. Peters S, Gettinger S, Johnson ML, Janne PA, Garassino MC, Christoph D, et al. Phase II trial of atezolizumab as first-line or subsequent therapy for patients with programmed death-ligand 1-selected advanced non-small-cell lung cancer (BIRCH). J Clin Oncol. 2017;35(24):2781–9.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. PACIFIC Investigators. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377(20):1919–29.

    Article  PubMed  CAS  Google Scholar 

  91. Greenhalgh J, Dwan K, Boland A, Bates V, Vecchio F, Dundar Y, et al. First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer. Cochrane Database Syst Rev. 2016;5:CD010383.

    Google Scholar 

  92. Paz-Ares L, Tan EH, O’Byrne K, Zhang L, Hirsh V, Boyer M, et al. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial. Ann Oncol. 2017;28(2):270–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. NHS Health Research Authority website. The ELDERS study—immunotherapy in elderly cancer patients. 2016. http://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/the-elders-study-immunotherapy-in-elderly-cancer-patients/. Accessed 05 Apr 2018.

  94. Gomes F, Woolley S, Califano R, Summers Y, Baker K, Burns K, et al. Elderly lung cancer patients on immunotherapy: preliminary results from the ELDERS study. J Thorac Oncol. 2017;12(11):S1841–2 (abstract no. MA 10.07).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester, M20 4BX, UK

    Fabio Gomes, Rebecca Tay, Jaseela Chiramel & Raffaele Califano

  2. Department of Medical Oncology, Manchester University NHS Foundation Trust, Manchester, UK

    Raffaele Califano

  3. Division of Cancer Sciences, University of Manchester, Manchester, UK

    Raffaele Califano

Authors
  1. Fabio Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rebecca Tay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jaseela Chiramel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Raffaele Califano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raffaele Califano.

Ethics declarations

Funding

No funding was used in the preparation of this review article.

Conflict of Interest

RC has received honoraria for consultancy and advisory boards from BMS, MSD, Roche, AstraZeneca/Medimmune, Takeda and Novartis; RC declares not owning any stock in any of these companies. FG, RT and JC declare that they have no conflicts of interest that might be relevant to the contents of this review.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gomes, F., Tay, R., Chiramel, J. et al. The Role of Targeted Agents and Immunotherapy in Older Patients with Non-small Cell Lung Cancer. Drugs Aging 35, 819–834 (2018). https://doi.org/10.1007/s40266-018-0573-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-018-0573-z

Search

Navigation