Advertisement

Lung Cancer in Older Adults: Systemic Treatment

  • Elisabeth Quoix
Living reference work entry

Abstract

Lung cancer is the first cause of death by cancer throughout the entire world. Its incidence increases with age, and thus median age at diagnosis is 70 years in the USA.

As in younger counterparts, non-small cell lung cancer represents 85% of the cases, but squamous cell carcinoma is more frequent than in younger patients. Diagnosis is often performed at an advanced stage, and thus systemic treatment is frequently to be discussed. It is only since two decades that clinical trials devoted to elderly patients have been conducted, and until recently, treatment was often suboptimal, with poor results which contributed to nihilistic attitudes among patients, relatives, and doctors.

Regarding small cell lung cancer, the doublet carboplatin-etoposide is the most frequently used in elderly patients. For non-small cell lung cancer, targeted therapies should be used in those patients with EGFR or V600E BRAF mutations and ALK or ROS1 translocations whatever the performance status (PS). For patients without targetable mutations, carboplatin-based doublet can be used as frontline therapy in patients with PS 0–2. Regarding second-line therapy, the most frequently studied in elderly patients has been erlotinib. The role of checkpoint inhibitors in elderly patients is still not well established as the only data we have are subgroup analyses of phase III randomized trials with no age upper limit and with no specific clinical trials.

Keywords

Lung cancer Elderly Chemotherapy Targeted therapy Immunotherapy 

References

  1. Abe T, Takeda K, Ohe Y, et al. Randomized phase III trial comparing weekly docetaxel plus cisplatin versus docetaxel monotherapy every 3 weeks in elderly patients with advanced non-small-cell lung cancer: the intergroup trial JCOG0803/WJOG4307L. J Clin Oncol. 2015;33:575–81.CrossRefPubMedGoogle Scholar
  2. Alberg AJ, Brock MV, Ford JG, Samet JM, Spivack SD. Epidemiology of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e1S–e29S.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ansari RH, Socinski MA, Edelman MJ, et al. A retrospective analysis of outcomes by age in a three-arm phase III trial of gemcitabine in combination with carboplatin or paclitaxel vs. paclitaxel plus carboplatin for advanced non-small cell lung cancer. Crit Rev Oncol Hematol. 2011;78:162–71.CrossRefPubMedGoogle Scholar
  4. Ardizzoni A, Favaretto A, Boni L, et al. Platinum-etoposide chemotherapy in elderly patients with small-cell lung cancer: results of a randomized multicenter phase II study assessing attenuated-dose or full-dose with lenograstim prophylaxis – a Forza Operativa Nazionale Italiana Carcinoma Polmonare and Gruppo Studio Tumori Polmonari Veneto (FONICAP-GSTPV) study. J Clin Oncol. 2005;23:569–75.CrossRefPubMedGoogle Scholar
  5. Auperin A, Le Pechoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:2181–90.CrossRefPubMedGoogle Scholar
  6. Azzoli CG, Temin S, Aliff T, et al. Focused update of 2009 American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol. 2011;29:3825–31.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Balducci L, Carreca I. The role of myelopoietic growth factors in managing cancer in the elderly. Drugs. 2002;62(Suppl 1):47–63.CrossRefPubMedGoogle Scholar
  8. Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist. 2000;5:224–37.CrossRefPubMedGoogle Scholar
  9. Barlesi F, Mazieres J, Merlio J-P, et al. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet. 2016;387:1415–26.CrossRefPubMedGoogle Scholar
  10. Belani CP, Lee JS, Socinski MA et al. Randomized phase III trial comparing cisplatin-etoposide to carboplatin-paclitaxel in advanced or metastatic non-small cell lung cancer. Ann Oncol 2005a;16(7):1069–75CrossRefPubMedGoogle Scholar
  11. Belani CP, Fossella F. Elderly subgroup analysis of a randomized phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for first-line treatment of advanced nonsmall cell lung carcinoma (TAX 326). Cancer. 2005b;104:2766–74.CrossRefPubMedGoogle Scholar
  12. Blanchard EM, Moon J, Hesketh PJ, et al. Comparison of platinum-based chemotherapy in patients older and younger than 70 years: an analysis of Southwest Oncology Group Trials 9308 and 9509. J Thorac Oncol. 2011;6:115–20.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–39.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–35.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Burdett S, Pignon JP, Tierney J, et al. Adjuvant chemotherapy for resected early-stage non-small cell lung cancer. Cochrane Database Syst Rev. 2015;2:CD011430.Google Scholar
  16. Caprario LC, Kent DM, Strauss GM. Effects of chemotherapy on survival of elderly patients with small-cell lung cancer: analysis of the SEER-medicare database. J Thorac Oncol. 2013;8:1272–81.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Chawla N, Yabroff KR, Mariotto A, McNeel TS, Schrag D, Warren JL. Limited validity of diagnosis codes in Medicare claims for identifying cancer metastases and inferring stage. Ann Epidemiol. 2014;24:666–672.e2.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Corre R, Greillier L, Le Caer 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;34:1476–83.CrossRefPubMedGoogle Scholar
  19. Eba J, Shimokawa T, Nakamura K, et al. A phase II/III study comparing carboplatin and irinotecan with carboplatin and etoposide for the treatment of elderly patients with extensive-disease small-cell lung cancer (JCOG1201). Jpn J Clin Oncol. 2015;45:115–8.CrossRefPubMedGoogle Scholar
  20. Ferrara R, Mezquita L, Auclin E, Chaput N, Besse B. Immunosenescence and immunecheckpoint inhibitors in non-small cell lung cancer patients: does age really matter? Cancer Treat Rev. 2017;60:60–8.CrossRefPubMedGoogle Scholar
  21. Frasci G, Lorusso V, Panza N, et al. Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000;18:2529–36.CrossRefPubMedGoogle Scholar
  22. Fruh M, Rolland E, Pignon JP, et al. Pooled analysis of the effect of age on adjuvant cisplatin-based chemotherapy for completely resected non-small-cell lung cancer. J Clin Oncol. 2008;26:3573–81.CrossRefPubMedGoogle Scholar
  23. Fukuda M, Soda H, Soejima Y, et al. A phase I trial of carboplatin and etoposide for elderly (>or=75 year-old) patients with small-cell lung cancer. Cancer Chemother Pharmacol. 2006;58:601–6.CrossRefPubMedGoogle Scholar
  24. Ganti AK, de Shazo M, Weir AB 3rd, Hurria A. Treatment of non-small cell lung cancer in the older patient. J Natl Compr Cancer Netw. 2012;10:230–9.CrossRefGoogle Scholar
  25. Gridelli C. The ELVIS trial: a phase III study of single-agent vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer. Elderly Lung Cancer Vinorelbine Italian Study. Oncologist. 2001;6(Suppl 1):4–7.CrossRefPubMedGoogle Scholar
  26. Gridelli C, Perrone F, Gallo C, et al. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003;95:362–72.CrossRefPubMedGoogle Scholar
  27. Gridelli C, de Marinis F, Thomas M, et al. Final efficacy and safety results of pemetrexed continuation maintenance therapy in the elderly from the PARAMOUNT phase III study. J Thorac Oncol. 2014;9:991–7.CrossRefPubMedGoogle Scholar
  28. Hamaker ME, Jonker JM, de Rooij SE, Vos AG, Smorenburg CH, van Munster BC. Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review. Lancet Oncol. 2012;13:e437–44.CrossRefPubMedGoogle Scholar
  29. Hanna N, Johnson D, Temin S, et al. Systemic therapy for stage IV non-small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2017;35:3484–515.CrossRefPubMedGoogle Scholar
  30. Herbst RS, Baas P, Kim DW, 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;387:1540–50.CrossRefPubMedGoogle Scholar
  31. Inoue Y, Inui N, Asada 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;76:155–61.CrossRefPubMedGoogle Scholar
  32. Jalal SI, Riggs HD, Melnyk A, et al. Updated survival and outcomes for older adults with inoperable stage III non-small-cell lung cancer treated with cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel: analysis of a phase III trial from the Hoosier Oncology Group (HOG) and US Oncology. Ann Oncol. 2012;23:1730–8.CrossRefPubMedGoogle Scholar
  33. Jett JR, Schild SE, Kesler KA, Kalemkerian GP. Treatment of small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e400S–19S.CrossRefPubMedGoogle Scholar
  34. Kudoh S, Takeda K, Nakagawa K, et al. Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol. 2006;24:3657–63.CrossRefPubMedGoogle Scholar
  35. Langer CJ, Manola J, Bernardo P, et al. Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: implications of Eastern Cooperative Oncology Group 5592, a randomized trial. J Natl Cancer Inst. 2002;94:173–81.CrossRefPubMedGoogle Scholar
  36. Larive S, Bombaron P, Riou R, et al. Carboplatin-etoposide combination in small cell lung cancer patients older than 70 years: a phase II trial. Lung Cancer. 2002;35:1–7.CrossRefPubMedGoogle Scholar
  37. Laskin J, Crinò L, Felip E, et al. Safety and efficacy of first-line bevacizumab plus chemotherapy in elderly patients with advanced or recurrent nonsquamous non-small cell lung cancer: safety of avastin in lung trial (MO19390). J Thorac Oncol. 2012;7:203–11.CrossRefPubMedGoogle Scholar
  38. Lees J, Chan A. Polypharmacy in elderly patients with cancer: clinical implications and management. Lancet Oncol. 2011;12:1249–57.CrossRefPubMedGoogle Scholar
  39. Leighl NB, Zatloukal P, Mezger J, et al. Efficacy and safety of bevacizumab-based therapy in elderly patients with advanced or recurrent nonsquamous non-small cell lung cancer in the phase III BO17704 study (AVAiL). J Thorac Oncol. 2010;5:1970–6.CrossRefPubMedGoogle Scholar
  40. Lilenbaum RC, Herndon JE 2nd, List MA, et al. Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730). J Clin Oncol. 2005;23:190–6.  https://doi.org/10.1200/JCO.2005.07.172.CrossRefPubMedGoogle Scholar
  41. Maione P, Perrone F, Gallo C, et al. Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study. J Clin Oncol. 2005;23:6865–72.CrossRefPubMedGoogle Scholar
  42. Masters GA, Temin S, Azzoli CG, et al. Systemic therapy for stage IV non-small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2015;33:3488–515.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Mellemgaard A, Luchtenborg M, Iachina M, et al. Role of comorbidity on survival after radiotherapy and chemotherapy for nonsurgically treated lung cancer. J Thorac Oncol. 2015;10:272–9.CrossRefPubMedGoogle Scholar
  44. Minuti G, D’Incecco A, Cappuzzo F. Current and emerging options in the management of EGFR mutation-positive non-small-cell lung cancer: considerations in the elderly. Drugs Aging. 2015;32:907–16.CrossRefPubMedGoogle Scholar
  45. Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ. 1995;311:899–909.CrossRefGoogle Scholar
  46. Okamoto H, Watanabe K, Kunikane H, et al. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007;97:162–9.CrossRefPubMedPubMedCentralGoogle Scholar
  47. Pallis AG, Gridelli C, van Meerbeeck JP, et al. EORTC Elderly Task Force and Lung Cancer Group and International Society for Geriatric Oncology (SIOG) experts’ opinion for the treatment of non-small-cell lung cancer in an elderly population. Ann Oncol. 2010a;21:692–706.CrossRefPubMedGoogle Scholar
  48. Pallis AG, Shepherd FA, Lacombe D, Gridelli C. Treatment of small-cell lung cancer in elderly patients. Cancer. 2010b;116:1192–200.CrossRefPubMedGoogle Scholar
  49. Pisters KMW, Evans WK, Azzoli CG, et al. Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages I–IIIA resectable non small-cell lung cancer guideline. J Clin Oncol. 2007;25:5506–18.CrossRefPubMedGoogle Scholar
  50. Quoix E, Breton JL, Daniel C, et al. Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study. Ann Oncol. 2001;12:957–62.CrossRefPubMedGoogle Scholar
  51. Quoix E, Zalcman G, Oster JP, et al. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011;378:1079–88.CrossRefPubMedGoogle Scholar
  52. Quoix E, Westeel V, Moreau L, et al. Second-line therapy in elderly patients with advanced nonsmall cell lung cancer. Eur Respir J. 2014;43:240–9.CrossRefPubMedGoogle Scholar
  53. Ramalingam SS, Dahlberg SE, Langer CJ, et al. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008;26:60–5.CrossRefPubMedGoogle Scholar
  54. Reck M, von Pawel J, Zatloukal P, et al. Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol. 2010;21:1804–9.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Repetto L, Fratino L, Audisio RA, et al. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. J Clin Oncol. 2002;20:494–502.CrossRefPubMedGoogle Scholar
  56. Sacher AG, Le LW, Leighl NB, Coate LE. Elderly patients with advanced NSCLC in phase III clinical trials: are the elderly excluded from practice-changing trials in advanced NSCLC? J Thorac Oncol. 2013;8:366–8.CrossRefPubMedGoogle Scholar
  57. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542–50.CrossRefPubMedGoogle Scholar
  58. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123–32.CrossRefPubMedGoogle Scholar
  59. Siegel R, Naishadham D, Jemal A. CA Cancer J Clin. 2012;62:10–29.CrossRefGoogle Scholar
  60. Soubeyran P, Bellera C, Goyard J, et al. Screening for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study. PLoS One. 2014;9:e115060.CrossRefPubMedPubMedCentralGoogle Scholar
  61. Souhami RL, Spiro SG, Rudd RM, et al. Five-day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy. J Natl Cancer Inst. 1997;89:577–80.CrossRefPubMedGoogle Scholar
  62. 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;22:4626–31.CrossRefPubMedGoogle Scholar
  63. Tomihara K, Curiel TJ, Zhang B. Optimization of immunotherapy in elderly cancer patients. Crit Rev Oncog. 2013;18:573–83.CrossRefPubMedPubMedCentralGoogle Scholar
  64. Tsukada H, Yokoyama A, Goto K, et al. Randomized controlled trial comparing docetaxel-cisplatin combination with weekly docetaxel alone in elderly patients with advanced non-small-cell lung cancer: Japan Clinical Oncology Group (JCOG) 0207dagger. Jpn J Clin Oncol. 2015;45:88–95.CrossRefPubMedGoogle Scholar
  65. Wang S, Wong M, Hamilton N, Davoren JB, Jahan TM, Walter LC. Impact of age and comorbidity on non-small-cell lung cancer treatment in older veterans. J Clin Oncol. 2012;30:1447–55.CrossRefPubMedPubMedCentralGoogle Scholar
  66. Westeel V, Murray N, Gelmon K, et al. New combination of the old drugs for elderly patients with small-cell lung cancer: a phase II study of the PAVE regimen. J Clin Oncol. 1998;16:1940–7.CrossRefPubMedGoogle Scholar
  67. 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;26:2350–7.CrossRefPubMedGoogle Scholar
  68. Yuen AR, Zou G, Turrisi AT, et al. Similar outcome of elderly patients in intergroup trial 0096: cisplatin, etoposide, and thoracic radiotherapy administered once or twice daily in limited stage small cell lung carcinoma. Cancer. 2000;89:1953–60.CrossRefPubMedGoogle Scholar
  69. Zukin M, Barrios CH, Pereira JR, et al. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol. 2013;31:2849–53.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Chest Diseases, Nouvel Hôpital CivilUniversity HospitalStrasbourgFrance

Section editors and affiliations

  • Etienne Brain
    • 1
  1. 1.Department of Medical Oncology, Institute CurieHôpital René HugueninSaint-CloudFrance

Personalised recommendations