SpringerLink
Log in

Systemic Therapy of Common Tumours in Older Patients: Challenges and Opportunities. A Young International Society of Geriatric Oncology Review Paper

  • Geriatric Oncology (L Balducci, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Decision-making for systemic treatments in older patients with cancer is difficult because of concerns for decreased organ function, risk of toxicity, limited life expectancy due to comorbidities and the lack of evidence available to guide its management in this population. Here, we review the data on the role of systemic agents for the treatment of common malignancies in this age group.

Recent Findings

Evidence on the use of systemic treatments for older patients with cancer is increasing, especially for newer options including immune checkpoint inhibitors and targeted agents that provide comparable benefit in older and younger patients. Nonetheless, the risks for short- and long-term toxicities need to be considered. More research is warranted and represents a unique opportunity to increase the knowledge on cancer treatment for older adults.

Summary

Healthy, older individuals should be considered for standard systemic treatment options, whereas those at risk based on geriatric assessments require adjusted plans. Geriatric assessments are key for decision-making.

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

Access this article

Log in via an institution

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Balducci L. Aging, frailty, and chemotherapy. Cancer Control. 2007;14(1):7–12.

    Article  PubMed  Google Scholar 

  2. Calcinotto A, Kohli J, Zagato E, Pellegrini L, Demaria M, Alimonti A. Cellular senescence: aging, cancer, and injury. Physiol Rev. 2019;99(2):1047–78.

    Article  CAS  PubMed  Google Scholar 

  3. Fulop T, et al. Frailty, inflammation and immunosenescence. Interdiscip Top Gerontol Geriatr. 2015;41:26–40.

    Article  PubMed  Google Scholar 

  4. **a S, et al. An update on inflamm-aging: mechanisms, prevention, and treatment. J Immunol Res. 2016;2016:8426874.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Abbasi J. Older patients (still) left out of cancer clinical trials. JAMA. 2019.

  6. Rocque GB, Williams GR. Bridging the data-free zone: decision making for older adults with cancer. J Clin Oncol. 2019:Jco1902588.

  7. Tack L, et al. Underrepresentation of vulnerable older patients with cancer in phase II and III oncology registration trials: a case-control study. J Geriatr Oncol. 2019.

  8. Liposits G, Loh KP, Soto-Perez-de-Celis E, Dumas L, Battisti NML, Kadambi S, et al. PARP inhibitors in older patients with ovarian and breast cancer: Young International Society of Geriatric Oncology review paper. J Geriatr Oncol. 2019;10(2):337–45.

    Article  PubMed  Google Scholar 

  9. • Loh KP, et al. What every oncologist should know about geriatric assessment for older patients with cancer: Young International Society of Geriatric Oncology position paper. J Oncol Pract. 2018;14(2):85–94 This comprehensive review outlines the relevance and the practicalities of geriatric assessments for the management of cancer in older patients.

    Article  PubMed  PubMed Central  Google Scholar 

  10. •• Mohile SG, et al. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol. 2018;36(22):2326–47 The ASCO guidelines are a key guidance including practical recommendations for the management of cancer in older patients.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Decoster L, van Puyvelde K, Mohile S, Wedding U, Basso U, Colloca G, et al. Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations. Ann Oncol. 2015;26(2):288–300.

    Article  CAS  PubMed  Google Scholar 

  12. Paillaud E, Soubeyran P, Caillet P, Cudennec T, Brain E, Terret C, et al. Multidisciplinary development of the Geriatric Core Dataset for clinical research in older patients with cancer: a French initiative with international survey. Eur J Cancer. 2018;103:61–8.

    Article  CAS  PubMed  Google Scholar 

  13. Wildiers H, Heeren P, Puts M, Topinkova E, Janssen-Heijnen MLG, Extermann M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014;32(24):2595–603.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Jolly TA, Deal AM, Nyrop KA, Williams GR, Pergolotti M, Wood WA, et al. Geriatric assessment-identified deficits in older cancer patients with normal performance status. Oncologist. 2015;20(4):379–85.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Repetto L, Fratino L, Audisio RA, Venturino A, Gianni W, Vercelli M, 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(2):494–502.

    Article  PubMed  Google Scholar 

  16. Hamaker ME, Wildes TM, Rostoft S. Time to stop saying geriatric assessment is too time consuming. J Clin Oncol. 2017;35(25):2871–4.

    Article  PubMed  Google Scholar 

  17. • Soto-Perez-de-Celis E, et al. Functional versus chronological age: geriatric assessments to guide decision making in older patients with cancer. Lancet Oncol. 2018;19(6):e305–16 This review highlights the role of geriatric assessments in evaluating the functional age of older cancer patients, which should be the main driver of decision-making rather than chronological age.

    Article  PubMed  Google Scholar 

  18. Decoster L, Kenis C, van Puyvelde K, Flamaing J, Conings G, de Grève J, et al. The influence of clinical assessment (including age) and geriatric assessment on treatment decisions in older patients with cancer. J Geriatr Oncol. 2013;4(3):235–41.

    Article  PubMed  Google Scholar 

  19. 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 

  20. Giantin V, Valentini E, Iasevoli M, Falci C, Siviero P, de Luca E, et al. Does the Multidimensional Prognostic Index (MPI), based on a Comprehensive Geriatric Assessment (CGA), predict mortality in cancer patients? Results of a prospective observational trial. J Geriatr Oncol. 2013;4(3):208–17.

    Article  PubMed  Google Scholar 

  21. Hamaker ME, Vos AG, Smorenburg CH, Rooij SE, Munster BC. The value of geriatric assessments in predicting treatment tolerance and all-cause mortality in older patients with cancer. Oncologist. 2012;17(11):1439–49.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hurria, A., A. Magnuson, and C.P. Gross. Development and validation of a chemotherapy toxicity (Chemo Tox) risk score for older patients (Pts) with breast cancer (BC) receiving adjuvant/neoadjuvant treatment (adjuvant Tx): a R01 and BCRF funded prospective multicenter study (Abstract GS6-04). In 2018 San Antonio Breast Cancer Symposium. 2018. San Antonio, TX, USA.

  23. 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 

  24. Klepin HD, Geiger AM, Tooze JA, Kritchevsky SB, Williamson JD, Pardee TS, et al. Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia. Blood. 2013;121(21):4287–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mohile SG, Velarde C, Hurria A, Magnuson A, Lowenstein L, Pandya C, et al. Geriatric assessment-guided care processes for older adults: a Delphi consensus of geriatric oncology experts. J Natl Compr Cancer Netw. 2015;13(9):1120–30.

    Article  Google Scholar 

  26. Dotan, E., et al., NCCN guidelines version 1.2019: older adult oncology. J Natl Compr Canc Netw, 2019.

  27. • Hamaker ME, et al. The effect of a geriatric evaluation on treatment decisions and outcome for older cancer patients - a systematic review. J Geriatr Oncol. 2018;9(5):430–40 In this paper, the authors outline the influence of geriatric assessment on decision-making and therapeutic outcomes in older patients with cancer.

    Article  PubMed  Google Scholar 

  28. Elkin EB, Hurria A, Mitra N, Schrag D, Panageas KS. Adjuvant chemotherapy and survival in older women with hormone receptor-negative breast cancer: assessing outcome in a population-based, observational cohort. J Clin Oncol. 2006;24(18):2757–64.

    Article  PubMed  Google Scholar 

  29. Giordano SH, Duan Z, Kuo YF, Hortobagyi GN, Goodwin JS. Use and outcomes of adjuvant chemotherapy in older women with breast cancer. J Clin Oncol. 2006;24(18):2750–6.

    Article  PubMed  Google Scholar 

  30. Fargeot P, Bonneterre J, Roché H, Lortholary A, Campone M, van Praagh I, et al. Disease-free survival advantage of weekly epirubicin plus tamoxifen versus tamoxifen alone as adjuvant treatment of operable, node-positive, elderly breast cancer patients: 6-year follow-up results of the French adjuvant study group 08 trial. J Clin Oncol. 2004;22(23):4622–30.

    Article  PubMed  CAS  Google Scholar 

  31. Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, et al. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009;360(20):2055–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Perrone F, Nuzzo F, di Rella F, Gravina A, Iodice G, Labonia V, et al. Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial. Ann Oncol. 2015;26(4):675–82.

    Article  CAS  PubMed  Google Scholar 

  33. von Minckwitz, G., T. Reimer, and J. Potenberg, The phase III ICE study: adjuvant ibandronate with or without capecitabine in elderly patients with moderate or high risk early breast cancer. Abstract S3-04, in 2014 San Antonio Breast Cancer Symposium. 2014.

  34. Barcenas CH, Niu J, Zhang N, Zhang Y, Buchholz TA, Elting LS, et al. Risk of hospitalization according to chemotherapy regimen in early-stage breast cancer. J Clin Oncol. 2014;32(19):2010–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Pinder MC, Duan Z, Goodwin JS, Hortobagyi GN, Giordano SH. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol. 2007;25(25):3808–15.

    Article  CAS  PubMed  Google Scholar 

  36. Rosenstock AS, Lei X, Tripathy D, Hortobagyi GN, Giordano SH, Chavez-MacGregor M. Short-term mortality in older patients treated with adjuvant chemotherapy for early-stage breast cancer. Breast Cancer Res Treat. 2016;157(2):339–50.

    Article  CAS  PubMed  Google Scholar 

  37. Muss HB, Woolf S, Berry D, Cirrincione C, Weiss RB, Budman D, et al. Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA. 2005;293(9):1073–81.

    Article  CAS  PubMed  Google Scholar 

  38. Brain EG, et al. Impact of liposomal doxorubicin-based adjuvant chemotherapy on autonomy in women over 70 with hormone-receptor-negative breast carcinoma: a French Geriatric Oncology Group (GERICO) phase II multicentre trial. Crit Rev Oncol Hematol. 2011;80(1):160–70.

    Article  PubMed  Google Scholar 

  39. Brouwers B, Hatse S, Lago LD, Neven P, Vuylsteke P, Dalmasso B, et al. The impact of adjuvant chemotherapy in older breast cancer patients on clinical and biological aging parameters. Oncotarget. 2016;7(21):29977–88.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Ibrahim NK, Frye DK, Buzdar AU, Walters RS, Hortobagyi GN. Doxorubicin-based chemotherapy in elderly patients with metastatic breast cancer. Tolerance and outcome. Arch Intern Med. 1996;156(8):882–8.

    Article  CAS  PubMed  Google Scholar 

  41. Bajetta E, Procopio G, Celio L, Gattinoni L, Della Torre S, Mariani L, et al. Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women. J Clin Oncol. 2005;23(10):2155–61.

    Article  CAS  PubMed  Google Scholar 

  42. Vogel C, O’Rourke M, Winer E, Hochster H, Chang A, Adamkiewicz B, et al. Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older. Ann Oncol. 1999;10(4):397–402.

    Article  CAS  PubMed  Google Scholar 

  43. Barni S, Livraghi L, Gravina A, Martella F, D’Onofrio L, Morritti M, et al. Feasibility of eribulin mesylate in older patients with locally advanced or metastatic breast cancer: a post-hoc analysis of the ESEMPiO study. J Geriatr Oncol. 2019;10(6):990–3.

    Article  PubMed  Google Scholar 

  44. Muss H, Cortes J, Vahdat LT, Cardoso F, Twelves C, Wanders J, et al. Eribulin monotherapy in patients aged 70 years and older with metastatic breast cancer. Oncologist. 2014;19(4):318–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Beuselinck B, Wildiers H, Wynendaele W, Dirix L, Kains JP, Paridaens R. Weekly paclitaxel versus weekly docetaxel in elderly or frail patients with metastatic breast carcinoma: a randomized phase-II study of the Belgian Society of Medical Oncology. Crit Rev Oncol Hematol. 2010;75(1):70–7.

    Article  PubMed  Google Scholar 

  46. Coleman RE, Biganzoli L, Canney P, Dirix L, Mauriac L, Chollet P, et al. A randomised phase II study of two different schedules of pegylated liposomal doxorubicin in metastatic breast cancer (EORTC-10993). Eur J Cancer. 2006;42(7):882–7.

    Article  CAS  PubMed  Google Scholar 

  47. Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552–9.

    Article  PubMed  Google Scholar 

  48. Pepe C, Hasan B, Winton TL, Seymour L, Graham B, Livingston RB, et al. Adjuvant vinorelbine and cisplatin in elderly patients: National Cancer Institute of Canada and Intergroup Study JBR.10. J Clin Oncol. 2007;25(12):1553–61.

    Article  CAS  PubMed  Google Scholar 

  49. Atagi S, Kawahara M, Yokoyama A, Okamoto H, Yamamoto N, Ohe Y, et al. Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol. 2012;13(7):671–8.

    Article  CAS  PubMed  Google Scholar 

  50. Hardy D, Liu CC, Cormier JN, **a R, du XL. Cardiac toxicity in association with chemotherapy and radiation therapy in a large cohort of older patients with non-small-cell lung cancer. Ann Oncol. 2010;21(9):1825–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Weiss GJ, Langer C, Rosell R, Hanna N, Shepherd F, Einhorn LH, et al. Elderly patients benefit from second-line cytotoxic chemotherapy: a subset analysis of a randomized phase III trial of pemetrexed compared with docetaxel in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2006;24(27):4405–11.

    Article  CAS  PubMed  Google Scholar 

  52. Hensing TA, Peterman AH, Schell MJ, Lee JH, Socinski MA. The impact of age on toxicity, response rate, quality of life, and survival in patients with advanced, stage IIIB or IV nonsmall cell lung carcinoma treated with carboplatin and paclitaxel. Cancer. 2003;98(4):779–88.

    Article  CAS  PubMed  Google Scholar 

  53. Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, 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(5):362–72.

    Article  CAS  PubMed  Google Scholar 

  54. 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.

    Article  CAS  PubMed  Google Scholar 

  55. Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, et al. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006;24(25):4085–91.

    Article  CAS  PubMed  Google Scholar 

  56. Hung A, Mullins CD. Relative effectiveness and safety of chemotherapy in elderly and nonelderly patients with stage III colon cancer: a systematic review. Oncologist. 2013;18(1):54–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Sargent DJ, Goldberg RM, Jacobson SD, Macdonald JS, Labianca R, Haller DG, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001;345(15):1091–7.

    Article  CAS  PubMed  Google Scholar 

  58. Twelves C, Scheithauer W, McKendrick J, Seitz JF, van Hazel G, Wong A, et al. Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy. Ann Oncol. 2012;23(5):1190–7.

    Article  CAS  PubMed  Google Scholar 

  59. Cheung WY, Renfro LA, Kerr D, de Gramont A, Saltz LB, Grothey A, et al. Determinants of early mortality among 37,568 patients with colon cancer who participated in 25 clinical trials from the Adjuvant Colon Cancer Endpoints Database. J Clin Oncol. 2016;34(11):1182–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Folprecht G, Cunningham D, Ross P, Glimelius B, di Costanzo F, Wils J, et al. Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol. 2004;15(9):1330–8.

    Article  CAS  PubMed  Google Scholar 

  61. Sastre J, Aranda E, Massutí B, Tabernero J, Chaves M, Abad A, et al. Elderly patients with advanced colorectal cancer derive similar benefit without excessive toxicity after first-line chemotherapy with oxaliplatin-based combinations: comparative outcomes from the 03-TTD-01 phase III study. Crit Rev Oncol Hematol. 2009;70(2):134–44.

    Article  PubMed  Google Scholar 

  62. Jackson NA, Barrueco J, Soufi-Mahjoubi R, Marshall J, Mitchell E, Zhang X, et al. Comparing safety and efficacy of first-line irinotecan/fluoropyrimidine combinations in elderly versus nonelderly patients with metastatic colorectal cancer: findings from the bolus, infusional, or capecitabine with camptostar-celecoxib study. Cancer. 2009;115(12):2617–29.

    Article  CAS  PubMed  Google Scholar 

  63. Feliu J, Safont MJ, Salud A, Losa F, García-Girón C, Bosch C, et al. Capecitabine and bevacizumab as first-line treatment in elderly patients with metastatic colorectal cancer. Br J Cancer. 2010;102(10):1468–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Cen P, Liu C, Du XL. Comparison of toxicity profiles of fluorouracil versus oxaliplatin regimens in a large population-based cohort of elderly patients with colorectal cancer. Ann Oncol. 2012;23(6):1503–11.

    Article  CAS  PubMed  Google Scholar 

  65. Stein BN, Petrelli NJ, Douglass HO, Driscoll DL, Arcangeli G, Meropol NJ. Age and sex are independent predictors of 5-fluorouracil toxicity. Analysis of a large scale phase III trial. Cancer. 1995;75(1):11–7.

    Article  CAS  PubMed  Google Scholar 

  66. Rothenberg ML, Cox JV, DeVore RF, Hainsworth JD, Pazdur R, Rivkin SE, et al. A multicenter, phase II trial of weekly irinotecan (CPT-11) in patients with previously treated colorectal carcinoma. Cancer. 1999;85(4):786–95.

    Article  CAS  PubMed  Google Scholar 

  67. Ho C, Ng K, O'Reilly S, Gill S. Outcomes in elderly patients with advanced colorectal cancer treated with capecitabine: a population-based analysis. Clin Colorectal Cancer. 2005;5(4):279–82.

    Article  PubMed  Google Scholar 

  68. Seymour MT, Thompson LC, Wasan HS, Middleton G, Brewster AE, Shepherd SF, et al. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet. 2011;377(9779):1749–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Dowsett M. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol. 2010;28(3):509–18.

    Article  CAS  PubMed  Google Scholar 

  70. Arraras JI, Illarramendi JJ, Manterola A, Asin G, Salgado E, Arrondo P, et al. Quality of life in elderly breast cancer patients with localized disease receiving endocrine treatment: a prospective study. Clin Transl Oncol. 2019;21(9):1231–9.

    Article  CAS  PubMed  Google Scholar 

  71. van de Water W, et al. Elderly postmenopausal patients with breast cancer are at increased risk for distant recurrence: a tamoxifen exemestane adjuvant multinational study analysis. Oncologist. 2013;18(1):8–13.

    Article  PubMed  Google Scholar 

  72. van de Water W, et al. Age-specific nonpersistence of endocrine therapy in postmenopausal patients diagnosed with hormone receptor-positive breast cancer: a TEAM study analysis. Oncologist. 2012;17(1):55–63.

    Article  PubMed  Google Scholar 

  73. Sammon JD, Abdollah F, Reznor G, Pucheril D, Choueiri TK, Hu JC, et al. Patterns of declining use and the adverse effect of primary androgen deprivation on all-cause mortality in elderly men with prostate cancer. Eur Urol. 2015;68(1):32–9.

    Article  PubMed  Google Scholar 

  74. Smith MR, Saad F, Egerdie B, Sieber PR, Tammela TLJ, Ke C, et al. Sarcopenia during androgen-deprivation therapy for prostate cancer. J Clin Oncol. 2012;30(26):3271–6.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Brollo J, Curigliano G, Disalvatore D, Marrone BF, Criscitiello C, Bagnardi V, et al. Adjuvant trastuzumab in elderly with HER-2 positive breast cancer: a systematic review of randomized controlled trials. Cancer Treat Rev. 2013;39(1):44–50.

    Article  CAS  PubMed  Google Scholar 

  76. Chavez-MacGregor M, Zhang N, Buchholz TA, Zhang Y, Niu J, Elting L, et al. Trastuzumab-related cardiotoxicity among older patients with breast cancer. J Clin Oncol. 2013;31(33):4222–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Vaz-Luis I, Keating NL, Lin NU, Lii H, Winer EP, Freedman RA. Duration and toxicity of adjuvant trastuzumab in older patients with early-stage breast cancer: a population-based study. J Clin Oncol. 2014;32(9):927–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Cetin B, Benekli M, Dane F, Boruban C, Gumus M, Oksuzoglu B, et al. Lapatinib plus capecitabine for HER2-positive advanced-stage breast cancer in elderly women: review of the Anatolian Society of Medical Oncology (ASMO) experience. Breast Care (Basel). 2013;8(1):67–70.

    Article  Google Scholar 

  79. Kaufman PA, Brufsky AM, Mayer M, Rugo HS, Tripathy D, Yood MU, et al. Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study. Breast Cancer Res Treat. 2012;135(3):875–83.

    Article  PubMed  PubMed Central  Google Scholar 

  80. • Wildiers H, et al. Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2-positive metastatic breast cancer (EORTC 75111-10114): an open-label, randomised, phase 2 trial from the Elderly Task Force/Breast Cancer Group. Lancet Oncol. 2018;19(3):323–36 This study addresses the management of advanced HER2-positive breast cancer with a novel regimen including a potentially safer combination of cytotoxics and targeted agents as opposed to the current standard of care which includes a chemotherapy regimen which might be challenging to deliver in this age group.

    Article  CAS  PubMed  Google Scholar 

  81. Freedman RA, Tolaney SM. Efficacy and safety in older patient subsets in studies of endocrine monotherapy versus combination therapy in patients with HR+/HER2- advanced breast cancer: a review. Breast Cancer Res Treat. 2018;167(3):607–14.

    Article  CAS  PubMed  Google Scholar 

  82. Howie LJ, et al. Outcomes of older women with hormone receptor-positive, human epidermal growth factor receptor-negative metastatic breast cancer treated with a CDK4/6 inhibitor and an aromatase inhibitor: an FDA pooled analysis. J Clin Oncol. 2019:Jco1802217.

  83. Pritchard, K.I., et al., Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2. Clin Breast Cancer, 2013. 13(6): p. 421–432.e8.

  84. 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  CAS  PubMed  Google Scholar 

  85. Wu YL, Sequist LV, Tan EH, Geater SL, Orlov S, Zhang L, et al. Afatinib as first-line treatment of older patients with EGFR mutation-positive non-small-cell lung cancer: subgroup analyses of the LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7 trials. Clin Lung Cancer. 2018;19(4):e465–79.

    Article  CAS  PubMed  Google Scholar 

  86. Cassidy J, Saltz LB, Giantonio BJ, Kabbinavar FF, Hurwitz HI, Rohr UP. Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. J Cancer Res Clin Oncol. 2010;136(5):737–43.

    Article  CAS  PubMed  Google Scholar 

  87. Pietrantonio F, Cremolini C, Aprile G, Lonardi S, Orlandi A, Mennitto A, et al. Single-agent panitumumab in frail elderly patients with advanced RAS and BRAF wild-type colorectal cancer: challenging drug label to light up new hope. Oncologist. 2015;20(11):1261–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hurwitz HI, Tebbutt NC, Kabbinavar F, Giantonio BJ, Guan ZZ, Mitchell L, et al. Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials. Oncologist. 2013;18(9):1004–12.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14(11):1077–85.

    Article  CAS  PubMed  Google Scholar 

  90. Tabernero J, van Cutsem E, Lakomý R, Prausová J, Ruff P, van Hazel GA, et al. Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Eur J Cancer. 2014;50(2):320–31.

    Article  CAS  PubMed  Google Scholar 

  91. Obermannova R, et al. Subgroup analysis in RAISE: a randomized, double-blind phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab or placebo in patients with metastatic colorectal carcinoma progression. Ann Oncol. 2016;27(11):2082–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Jehn CF, Böning L, Kröning H, Possinger K, Lüftner D. Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer. Br J Cancer. 2012;106(2):274–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Van Cutsem E, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007;25(13):1658–64.

    Article  PubMed  CAS  Google Scholar 

  94. Meyerhardt JA, Li L, Sanoff HK, Carpenter W IV, Schrag D. Effectiveness of bevacizumab with first-line combination chemotherapy for Medicare patients with stage IV colorectal cancer. J Clin Oncol. 2012;30(6):608–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Tsai HT, Marshall JL, Weiss SR, Huang CY, Warren JL, Freedman AN, et al. Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study. Ann Oncol. 2013;24(6):1574–9.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Aparicio T, Bouché O, Taieb J, Maillard E, Kirscher S, Etienne PL, et al. Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial-PRODIGE 20 study results. Ann Oncol. 2018;29(1):133–8.

    Article  CAS  PubMed  Google Scholar 

  97. Sastre J, Grávalos C, Rivera F, Massuti B, Valladares-Ayerbes M, Marcuello E, et al. First-line cetuximab plus capecitabine in elderly patients with advanced colorectal cancer: clinical outcome and subgroup analysis according to KRAS status from a Spanish TTD Group Study. Oncologist. 2012;17(3):339–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Betof AS, Nipp RD, Giobbie-Hurder A, Johnpulle RAN, Rubin K, Rubinstein SM, et al. Impact of age on outcomes with immunotherapy for patients with melanoma. Oncologist. 2017;22(8):963–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Nishijima TF, Muss HB, Shachar SS, Moschos SJ. Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: a systematic review and meta-analysis. Cancer Treat Rev. 2016;45:30–7.

    Article  CAS  PubMed  Google Scholar 

  100. Chiarion Sileni V, Pigozzo J, Ascierto PA, Grimaldi AM, Maio M, di Guardo L, et al. Efficacy and safety of ipilimumab in elderly patients with pretreated advanced melanoma treated at Italian centres through the expanded access programme. J Exp Clin Cancer Res. 2014;33:30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Friedman CF, et al. Efficacy and safety of checkpoint blockade for treatment of advanced melanoma (mel) in patients (pts) age 80 and older (80+). Journal of Clinical Oncology. 2016;34(15_suppl):10009–10009.

    Google Scholar 

  102. Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, 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  CAS  PubMed  Google Scholar 

  103. Reck M, Rodríguez–Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. 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. J Clin Oncol. 2019;37(7):537–46.

    Article  CAS  PubMed  Google Scholar 

  104. Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, et al. 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. 2019;393(10183):1819–30.

    Article  CAS  PubMed  Google Scholar 

  105. Nosaki K, Saka H, Hosomi Y, Baas P, de Castro G Jr, Reck M, et al. Safety and efficacy of pembrolizumab monotherapy in elderly patients with PD-L1-positive advanced non-small-cell lung cancer: pooled analysis from the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 studies. Lung Cancer. 2019;135:188–95.

    Article  PubMed  Google Scholar 

  106. Vokes EE, Ready N, Felip E, Horn L, Burgio MA, Antonia SJ, et al. Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases. Ann Oncol. 2018;29(4):959–65.

    Article  CAS  PubMed  Google Scholar 

  107. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. 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 

  108. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342–50.

    Article  CAS  PubMed  Google Scholar 

  109. 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  CAS  PubMed  Google Scholar 

  110. Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018;379(21):2040–51.

    Article  CAS  PubMed  Google Scholar 

  111. Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288–301.

    Article  CAS  PubMed  Google Scholar 

  112. West H, McCleod M, Hussein M, Morabito A, Rittmeyer A, Conter HJ, et al. 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. Lancet Oncol. 2019;20(7):924–37.

    Article  CAS  PubMed  Google Scholar 

  113. F. Barlesi, M.N., M. Cobo, N. Steele, V. Paramonov, B. Parente, R. Dear, H. Berard, N. Peled, L.C. Seneviratne, E. Baldini, S. Watanabe, K. Goto, D. Mendus, H. Patel, Y. Deng, M. Kowanetz, T. Hoang18, W. Lin, V.A. Papadimitrakopoulou. IMpower132: efficacy of atezolizumab + carboplatin/cisplatin + pemetrexed as 1L treatment in key subgroups with stage IV non-squamous NSCLC. In European Society for Medical Oncology 2018 Congress. 2019. Munich, Germany.

  114. Jotte, R.M., et al., IMpower131: primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC. Journal of Clinical Oncology, 2018. 36(18_suppl): p. LBA9000-LBA9000.

  115. Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116–27.

    Article  CAS  PubMed  Google Scholar 

  116. Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1103–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol. 2009;27(8):1177–83.

    Article  CAS  PubMed  Google Scholar 

  118. de Glas NA, Bastiaannet E, Engels CC, de Craen AJM, Putter H, van de Velde CJH, et al. Validity of the online PREDICT tool in older patients with breast cancer: a population-based study. Br J Cancer. 2016;114(4):395–400.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Schneider M, Zuckerman IH, Onukwugha E, Pandya N, Seal B, Gardner J, et al. Chemotherapy treatment and survival in older women with estrogen receptor-negative metastatic breast cancer: a population-based analysis. J Am Geriatr Soc. 2011;59(4):637–46.

    Article  PubMed  Google Scholar 

  120. Wisnivesky JP, Smith CB, Packer S, Strauss GM, Lurslurchachai L, Federman A, et al. Survival and risk of adverse events in older patients receiving postoperative adjuvant chemotherapy for resected stages II-IIIA lung cancer: observational cohort study. BMJ. 2011;343:d4013.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Fruh M, 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(21):3573–81.

    Article  CAS  PubMed  Google Scholar 

  122. Miller ED, Fisher JL, Haglund KE, Grecula JC, Xu-Welliver M, Bertino EM, et al. The addition of chemotherapy to radiation therapy improves survival in elderly patients with stage III non-small cell lung cancer. J Thorac Oncol. 2018;13(3):426–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Belderbos, J., et al., The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R): real-world data on elderly stage III non-small cell lung cancer treated with definitive chemoradiation. International Journal of Radiation Oncology*Biology*Physics, 2019. 105(1, Supplement): p. S45-S46.

  124. Ryan KJ, Skinner KE, Fernandes AW, Punekar RS, Pavilack M, Walker MS, et al. Real-world treatment patterns among patients with unresected stage III non-small-cell lung cancer. Future Oncol. 2019;15(25):2943–53.

    Article  CAS  PubMed  Google Scholar 

  125. Auperin A, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28(13):2181–90.

    Article  CAS  PubMed  Google Scholar 

  126. Abe T, Takeda K, Ohe Y, Kudoh S, Ichinose Y, Okamoto H, 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(6):575–81.

    Article  CAS  PubMed  Google Scholar 

  127. Lilenbaum R, Villaflor VM, Langer C, O’Byrne K, O’Brien M, Ross HJ, et al. Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2: prognostic factors and treatment selection based on two large randomized clinical trials. J Thorac Oncol. 2009;4(7):869–74.

    Article  PubMed  Google Scholar 

  128. Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, 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(9796):1079–88.

    Article  CAS  PubMed  Google Scholar 

  129. Zukin M, Barrios CH, Rodrigues Pereira J, de Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, 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(23):2849–53.

    Article  CAS  PubMed  Google Scholar 

  130. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. The Elderly Lung Cancer Vinorelbine Italian Study Group. J Natl Cancer Inst. 1999;91(1):66–72.

  131. Kudoh S, Takeda K, Nakagawa K, Takada M, Katakami N, Matsui 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(22):3657–63.

    Article  CAS  PubMed  Google Scholar 

  132. Andre T, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27(19):3109–16.

    Article  CAS  PubMed  Google Scholar 

  133. Iveson T, et al. Prospective pooled analysis of four randomized trials investigating duration of adjuvant (adj) oxaliplatin-based therapy (3 vs 6 months {m}) for patients (pts) with high-risk stage II colorectal cancer (CC). Journal of Clinical Oncology. 2019;37(15_suppl):3501–3501.

    Article  Google Scholar 

  134. Meyers BM, Cosby R, Quereshy F, Jonker D. Adjuvant chemotherapy for stage II and III colon cancer following complete resection: a Cancer Care Ontario systematic review. Clin Oncol (R Coll Radiol). 2017;29(7):459–65.

    Article  CAS  Google Scholar 

  135. Weiser MR, Landmann RG, Kattan MW, Gonen M, Shia J, Chou J, et al. Individualized prediction of colon cancer recurrence using a nomogram. J Clin Oncol. 2008;26(3):380–5.

    Article  PubMed  Google Scholar 

  136. D'Andre S, Sargent DJ, Cha SS, Buroker TR, Kugler JW, Goldberg RM, et al. 5-Fluorouracil-based chemotherapy for advanced colorectal cancer in elderly patients: a north central cancer treatment group study. Clin Colorectal Cancer. 2005;4(5):325–31.

    Article  CAS  PubMed  Google Scholar 

  137. • Winther SB, et al. Reduced-dose combination chemotherapy (S-1 plus oxaliplatin) versus full-dose monotherapy (S-1) in older vulnerable patients with metastatic colorectal cancer (NORDIC9): a randomised, open-label phase 2 trial. Lancet Gastroenterol Hepatol. 2019;4(5):376–88 This paper presents a study specifically addressing the management advanced colorectal cancer, a common malignancy, in a population of older and vulnerable patients, that resemble more closely those seen in routine practice.

    Article  PubMed  Google Scholar 

  138. • de Glas N, et al. Improved survival of older patients with advanced breast cancer due to an increase in systemic treatments: a population-based study. Breast Cancer Res Treat. 2019;178(1):141–9 This study outlines the impact of changes in the use of systemic treatments on the survival of older patients with breast cancer.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Derks MGM, Bastiaannet E, van de Water W, de Glas NA, Seynaeve C, Putter H, et al. Impact of age on breast cancer mortality and competing causes of death at 10 years follow-up in the adjuvant TEAM trial. Eur J Cancer. 2018;99:1–8.

    Article  CAS  PubMed  Google Scholar 

  140. Droz JP, Albrand G, Gillessen S, Hughes S, Mottet N, Oudard S, et al. Management of prostate cancer in elderly patients: recommendations of a task force of the International Society of Geriatric Oncology. Eur Urol. 2017;72(4):521–31.

    Article  PubMed  Google Scholar 

  141. VanderWalde A, Hurria A. Aging and osteoporosis in breast and prostate cancer. CA Cancer J Clin. 2011;61(3):139–56.

    Article  PubMed  Google Scholar 

  142. Krasnova A, Epstein M, Marchese M, Dickerman BA, Cole AP, Lipsitz SR, et al. Risk of dementia following androgen deprivation therapy for treatment of prostate cancer. Prostate Cancer Prostatic Dis. 2019.

  143. Rugo HS, Turner NC, Finn RS, Joy AA, Verma S, Harbeck N, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123–33.

    Article  CAS  PubMed  Google Scholar 

  144. • Battisti NML, et al. Use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in older patients with ER-positive HER2-negative breast cancer: Young International Society of Geriatric Oncology review paper. Ther Adv Med Oncol. 2018;(10):1758835918809610 This review summarizes the data available on the use of CDK4/6 inhibitors, that have radically changed the treatment paradigm of advanced luminal breast cancer, in older patients, outlining also the ongoing research on the topic.

  145. Andre F, et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019;380(20):1929–40.

    Article  CAS  PubMed  Google Scholar 

  146. Owusu, C., et al., Safety and efficacy of single-agent adjuvant trastzumab in older women with breast cancer. Journal of Clinical Oncology, 2011. 29(15_suppl): p. TPS109-TPS109.

  147. von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377(2):122–31.

    Article  Google Scholar 

  148. Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(12):1688–700.

    Article  CAS  PubMed  Google Scholar 

  149. von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617–28.

    Article  Google Scholar 

  150. Soto-Perez-De-Celis E, et al. Targeted agents for HER2-positive breast cancer in older adults: current and future perspectives. Expert Opin Investig Drugs. 2018;27(10):787–801.

    Article  CAS  PubMed  Google Scholar 

  151. Losanno T, Gridelli C. Recent advances in targeted advanced lung cancer therapy in the elderly. Expert Rev Anticancer Ther. 2017;17(9):787–97.

    Article  CAS  PubMed  Google Scholar 

  152. Y. Takeyasu, Y.G., R. Morita, J. Sato, S. Murakami, H. Horinouchi, Y. Fujiwara, S. Kanda, N. Yamamoto, Y. Ohe. Efficacy and safety of epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKI) in elderly patients with EGFR mutation-positive NSCLC. in European Society for Medical Oncology Asia 2018 Congress. 2018. Singapore, Singapore.

  153. Papamichael D, Audisio RA, Glimelius B, de Gramont A, Glynne-Jones R, Haller D, et al. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol. 2015;26(3):463–76.

    Article  CAS  PubMed  Google Scholar 

  154. Bouchahda M, Macarulla T, Spano JP, Bachet JB, Lledo G, Andre T, et al. Cetuximab efficacy and safety in a retrospective cohort of elderly patients with heavily pretreated metastatic colorectal cancer. Crit Rev Oncol Hematol. 2008;67(3):255–62.

    Article  CAS  PubMed  Google Scholar 

  155. Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol. 2015;33(17):1889–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30.

    Article  CAS  PubMed  Google Scholar 

  157. Larkin J, Minor D, D’Angelo S, Neyns B, Smylie M, Miller WH Jr, et al. Overall survival in patients with advanced melanoma who received nivolumab versus investigator’s choice chemotherapy in CheckMate 037: a randomized, controlled, open-label phase III trial. J Clin Oncol. 2018;36(4):383–90.

    Article  CAS  PubMed  Google Scholar 

  158. Schachter J, Ribas A, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017;390(10105):1853–62.

    Article  CAS  PubMed  Google Scholar 

  159. Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16(8):908–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381(16):1535–46.

    Article  CAS  PubMed  Google Scholar 

  161. Elias R, Giobbie-Hurder A, McCleary NJ, Ott P, Hodi FS, Rahma O. Efficacy of PD-1 & PD-L1 inhibitors in older adults: a meta-analysis. J Immunother Cancer. 2018;6(1):26.

    Article  PubMed  PubMed Central  Google Scholar 

  162. • Bastiaannet E, et al. Immunotherapy and targeted therapies in older patients with advanced melanoma; Young International Society of Geriatric Oncology review paper. J Geriatr Oncol. 2019;10(3):389–97 This review summarizes the data available on the use of immunotherapy and targeted agents in older patients with advanced melanoma, whose prognosis has changed substantially following the introduction of a number of new agents although data in this age group are still lacking.

    Article  PubMed  Google Scholar 

  163. 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  CAS  PubMed  PubMed Central  Google Scholar 

  164. Bordoni, R., et al., Patient-reported outcomes in OAK: a phase III study of atezolizumab versus docetaxel in advanced non-small-cell lung cancer. Clin Lung Cancer, 2018. 19(5): p. 441–449.e4.

  165. Muchnik E, Loh KP, Strawderman M, Magnuson A, Mohile SG, Estrah V, et al. Immune checkpoint inhibitors in real-world treatment of older adults with non-small cell lung cancer. J Am Geriatr Soc. 2019;67(5):905–12.

    Article  PubMed  PubMed Central  Google Scholar 

  166. Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V, et al. Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v58–68.

    Article  CAS  PubMed  Google Scholar 

  167. Motzer RJ, Rini BI, McDermott D, Arén Frontera O, Hammers HJ, Carducci MA, et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol. 2019;20(10):1370–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019;393(10189):2404–15.

    Article  PubMed  Google Scholar 

  169. Denlinger CS, Sanft T, Baker KS, Broderick G, Demark-Wahnefried W, Friedman DL, et al. Survivorship, version 2.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2018;16(10):1216–47.

    Article  CAS  Google Scholar 

  170. Shapiro CL. Cancer survivorship. N Engl J Med. 2018;379(25):2438–50.

    Article  PubMed  Google Scholar 

  171. Runowicz CD, Leach CR, Henry NL, Henry KS, Mackey HT, Cowens-Alvarado RL, et al. American Cancer Society/American Society of Clinical Oncology breast cancer survivorship care guideline. J Clin Oncol. 2016;34(6):611–35.

    Article  CAS  PubMed  Google Scholar 

  172. Resnick MJ, Lacchetti C, Penson DF. Prostate cancer survivorship care guidelines: American Society of Clinical Oncology practice guideline endorsement. J Oncol Pract. 2015;11(3):e445–9.

    Article  PubMed  Google Scholar 

  173. Khatcheressian JL, Hurley P, Bantug E, Esserman LJ, Grunfeld E, Halberg F, et al. Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31(7):961–5.

    Article  CAS  PubMed  Google Scholar 

  174. Rowland JH, Bellizzi KM. Cancer survivorship issues: life after treatment and implications for an aging population. J Clin Oncol. 2014;32(24):2662–8.

    Article  PubMed  PubMed Central  Google Scholar 

  175. Shapiro CL, van Poznak C, Lacchetti C, Kirshner J, Eastell R, Gagel R, et al. Management of osteoporosis in survivors of adult cancers with nonmetastatic disease: ASCO clinical practice guideline. J Clin Oncol. 2019;37(31):2916–46.

    Article  PubMed  Google Scholar 

  176. Cauley JA, Giangregorio L. Physical activity and skeletal health in adults. Lancet Diabetes Endocrinol. 2019.

  177. Berger AM, Mooney K, Alvarez-Perez A, Breitbart WS, Carpenter KM, Cella D, et al. Cancer-related fatigue, version 2.2015. J Natl Compr Cancer Netw. 2015;13(8):1012–39.

    Article  Google Scholar 

  178. Ebede CC, Jang Y, Escalante CP. Cancer-related fatigue in cancer survivorship. Med Clin North Am. 2017;101(6):1085–97.

    Article  PubMed  Google Scholar 

  179. Bower JE, Bak K, Berger A, Breitbart W, Escalante CP, Ganz PA, et al. Screening, assessment, and management of fatigue in adult survivors of cancer: an American Society of Clinical Oncology clinical practice guideline adaptation. J Clin Oncol. 2014;32(17):1840–50.

    Article  PubMed  PubMed Central  Google Scholar 

  180. Magnuson A, Mohile S, Janelsins M. Cognition and cognitive impairment in older adults with cancer. Curr Geriatr Rep. 2016;5(3):213–9.

    Article  PubMed  PubMed Central  Google Scholar 

  181. Lange M, et al. Cancer-related cognitive impairment: an update on state of the art, detection, and management strategies in cancer survivors. Ann Oncol. 2019.

  182. Loh KP, Janelsins MC, Mohile SG, Holmes HM, Hsu T, Inouye SK, et al. Chemotherapy-related cognitive impairment in older patients with cancer. J Geriatr Oncol. 2016;7(4):270–80.

    Article  PubMed  PubMed Central  Google Scholar 

  183. Pergolotti M, et al. Embracing the complexity: older adults with cancer-related cognitive decline-a Young International Society of Geriatric Oncology position paper. J Geriatr Oncol. 2019.

  184. Cavaletti, G., P. Alberti, and P. Marmiroli, Chemotherapy-induced peripheral neurotoxicity in cancer survivors: an underdiagnosed clinical entity? Am Soc Clin Oncol Educ Book, 2015: p. e553–60.

  185. Hershman DL, Lacchetti C, Loprinzi CL. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline summary. J Oncol Pract. 2014;10(6):e421–4.

    Article  PubMed  Google Scholar 

  186. Marshall TF, Zipp GP, Battaglia F, Moss R, Bryan S. Chemotherapy-induced-peripheral neuropathy, gait and fall risk in older adults following cancer treatment. Journal of Cancer Research and Practice. 2017;4(4):134–8.

    Article  Google Scholar 

  187. Kalsi T, Babic-Illman G, Fields P, Hughes S, Maisey N, Ross P, et al. The impact of low-grade toxicity in older people with cancer undergoing chemotherapy. Br J Cancer. 2014;111(12):2224–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Lackman M, Vickers MM, Hsu T. Physician-reported reasons for non-enrollment of older adults in cancer clinical trials. J Geriatr Oncol. 2019.

  189. Sedrak MS, et al. Barriers to clinical trial enrollment of older adults with cancer: a qualitative study of the perceptions of community and academic oncologists. J Geriatr Oncol. 2019.

Download references

Acknowledgements

Dr. Battisti wishes to acknowledge the support of The Royal Marsden NIHR Biomedical Research Centre for Cancer and The Cridlan Ross Smith Charitable Trust.

Funding

Dr. Mohile is funded in part by a mid-career development award from the National Institutes on Aging (K24AG056589). The other authors have no funding to report.

Author information

Author notes

  1. Nicolò Matteo Luca Battisti and Gabor Liposits contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, UK

    Nicolò Matteo Luca Battisti

  2. Breast Cancer Research Division, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, UK

    Nicolò Matteo Luca Battisti

  3. Department of Oncology, Regional Hospital West Jutland, Gl Landevej 61, 7400, Herning, Denmark

    Gabor Liposits

  4. Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333, Leiden, ZA, Netherlands

    Nienke Aafke De Glas

  5. Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK

    Fabio Gomes

  6. Drug Development Department, Institut Gustave Roussy, Gustave Roussy Cancer Campus, 114 Rue Edouard Vaillant, 94800, Villejuif, France

    Capucine Baldini

  7. Division of Hematology/Oncology, James P. Wilmot Cancer Institute, University of Rochester Medical Center, 601 Elmwood Ave # 704, Rochester, NY, 14642, USA

    Supriya Mohile

Authors
  1. Nicolò Matteo Luca Battisti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabor Liposits
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nienke Aafke De Glas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fabio Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Capucine Baldini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Supriya Mohile
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicolò Matteo Luca Battisti.

Ethics declarations

Conflict of Interest

Dr. Battisti has received travel grants from Genomic Health and Pfizer and speaker fees from Pfizer. Dr. Mohile has received research funding from Carevive. The other authors have no disclosures.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Geriatric Oncology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Battisti, N.M.L., Liposits, G., De Glas, N.A. et al. Systemic Therapy of Common Tumours in Older Patients: Challenges and Opportunities. A Young International Society of Geriatric Oncology Review Paper. Curr Oncol Rep 22, 98 (2020). https://doi.org/10.1007/s11912-020-00958-z

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11912-020-00958-z

Keywords

Search

Navigation