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Immunotherapy in Older Patients with Advanced Melanoma: A Review of the Current Evidence

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Abstract

Despite the increasing incidence of metastatic melanoma in the older population, there is relatively limited specific data surrounding the use of immunotherapy for the treatment of advanced melanoma for patients above the age of 65 years. To date, there has not been a prospective trial done to evaluate the safety and efficacy of using immunotherapy to treat older patients with advanced melanoma. Older patients are often under-represented in clinical trials. In addition, older patients in clinical trials may have lower Eastern Cooperative Oncology Group (ECOG) performance score and fewer co-morbidities, and thus trial data may not truly reflect the experience of treating older patients. The purpose of this descriptive review is to examine the efficacy and safety data of the three currently approved immune checkpoint inhibitors for advanced melanoma treatment in older patients. Our review of available data established that the efficacy and tolerability of immunotherapy in older patients are comparable to results seen in younger patients. However, a dedicated, prospective, randomised trial to assess the safety, tolerability, and quality-of-life parameters of immunotherapy in the older population would provide further insight on the value of these treatments.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. 2018;68:394–424.

    Article  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.

    Article  PubMed  Google Scholar 

  3. Curchin DJ, Harris VR, McCormack CJ, Smith SD. Changing trends in the incidence of invasive melanoma in Victoria, 1985–2015. Med J Aust. 2018;208:265–9.

    Article  PubMed  Google Scholar 

  4. Guy GP Jr, Thomas CC, Thompson T, Watson M, Massetti GM, Richardson LC. Vital signs: melanoma incidence and mortality trends and projections—United States, 1982–2030. MMWR Morb Mortal Wkly Rep. 2015;64:591–6.

    PubMed  PubMed Central  Google Scholar 

  5. Malaguarnera L, Cristaldi E, Malaguarnera M. The role of immunity in elderly cancer. Crit Rev Oncol Hematol. 2010;74:40–60.

    Article  PubMed  Google Scholar 

  6. Berger NA, Savvides P, Koroukian SM, et al. Cancer in the elderly. Trans Am Clin Climatol Assoc. 2006;117:147–56.

    PubMed  PubMed Central  Google Scholar 

  7. Lewis JH, Kilgore ML, Goldman DP, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol. 2003;21:1383–9.

    Article  PubMed  Google Scholar 

  8. Townsley CA, Selby R, Siu LL. Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol. 2005;23:3112–244.

    Article  PubMed  Google Scholar 

  9. Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25:1824–31.

    Article  PubMed  Google Scholar 

  10. Hurria A, Dale W, Mooney M, et al. Designing therapeutic clinical trials for older and frail adults with cancer: U13 conference recommendations. J Clin Oncol. 2014;32:2587–94.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Festino L, Vanella V, Strudel M, Ascierto PA. Chapter 7—molecular mechanisms underlying the action of ipilimumab against metastatic melanoma. In: Hayat MA, editor. Immunology. San Diego: Academic Press; 2018. p. 85–96.

    Chapter  Google Scholar 

  12. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364:2517–26.

    Article  CAS  PubMed  Google Scholar 

  14. Ascierto PA, Del Vecchio M, Robert C, et al. Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2017;18:611–22.

    Article  CAS  PubMed  Google Scholar 

  15. Raedler LA. Keytruda (pembrolizumab): first PD-1 inhibitor approved for previously treated unresectable or metastatic melanoma. Am Health Drug Benefits. 2015;8:96–100.

    PubMed  PubMed Central  Google Scholar 

  16. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ivashko IN, Kolesar JM. Pembrolizumab and nivolumab: PD-1 inhibitors for advanced melanoma. Am J Health Syst Pharm. 2016;73:193–201.

    Article  CAS  PubMed  Google Scholar 

  19. Australian Product Infrmation Opdivo (Nivolumab). AU_PI_OPDIVO_V20.0 ed.

  20. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–30.

    Article  CAS  PubMed  Google Scholar 

  21. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372:2006–177.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lebbé C, Meyer N, Mortier L, et al. Evaluation of two dosing regimens for nivolumab in combination with ipilimumab in patients with advanced melanoma: results from the phase IIIb/IV CheckMate 511 Trial. J Clin Oncol. 2019;37:867–75.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mian I, Yang M, Zhao H, et al. Immune-related adverse events and survival in elderly patients with melanoma treated with ipilimumab. J Clin Oncol. 2016;34:3047–3047.

    Article  Google Scholar 

  25. Shaw AC, Trinh V, Bassett RL, et al. Retrospective analysis of safety and efficacy of ipilimumab in elderly patients with advanced melanoma. J Clin Oncol. 2016;34:9540–9540.

    Article  Google Scholar 

  26. Chandra S, Madden KM, Kannan R, Pavlick AC. Evaluating the safety of anti-CTLA-4 therapy in the elderly with unresectable melanoma. J Clin Oncol. 2013;31:9063.

    Article  Google Scholar 

  27. Leroy V, Gerard E, Dutriaux C, et al. Adverse events need for hospitalization and systemic immunosuppression in very elderly patients (over 80 years) treated with ipilimumab for metastatic melanoma. Cancer Immunol Immunother CII. 2019;68:545–51.

    Article  CAS  PubMed  Google Scholar 

  28. Chiarion Sileni V, Pigozzo J, Ascierto PA, 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;33:30–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Berrocal A, Arance A, Lopez Martin JA, et al. Ipilimumab for advanced melanoma: experience from the Spanish expanded access program. Melanoma Res. 2014;24:577–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Betof AS, Nipp RD, Giobbie-Hurder A, et al. Impact of age on outcomes with immunotherapy for patients with melanoma. Oncologist. 2017;22:963–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kugel CH 3rd, Douglass SM, Webster MR, et al. Age correlates with response to anti-PD1, reflecting age-related differences in intratumoral effector and regulatory T-cell populations. Clin Cancer Res. 2018;24:5347–56.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ben-Betzalel G, Steinberg-Silman Y, Stoff R, et al. Immunotherapy comes of age in octagenarian and nonagenarian metastatic melanoma patients. Eur J Cancer (Oxford, England: 1990). 2019;108:61–8.

    Article  Google Scholar 

  33. Chanal J, Kramkimel N, Ratour C, Aractingi S, Guegan S, Avril MF. Pembrolizumab for unresectable or metastatic melanoma in patients older than 85 years of age. Dermatology (Basel, Switzerland). 2019;235:219–24.

    Article  CAS  Google Scholar 

  34. Perier-Muzet M, Gatt E, Peron J, et al. Association of immunotherapy with overall survival in elderly patients with melanoma. JAMA Dermatol. 2018;154:82–7.

    Article  PubMed  Google Scholar 

  35. Ibrahim T, Mateus C, Baz M, Robert C. Older melanoma patients aged 75 and above retain responsiveness to anti-PD1 therapy: results of a retrospective single-institution cohort study. Cancer Immunol Immunother CII. 2018;67:1571–8.

    Article  CAS  PubMed  Google Scholar 

  36. Zhang S, Samani A, Spiers L, et al. The impact of patient age on toxicity and efficacy of immunotherapy agents. J Clin Oncol. 2018;36:e15116–e1511615116.

    Article  Google Scholar 

  37. Sattar J, Kartolo A, Hopman WM, Lakoff JM, Baetz T. The efficacy and toxicity of immune checkpoint inhibitors in a real-world older patient population. J Geriatr Oncol. 2019;10:411–4.

    Article  PubMed  Google Scholar 

  38. Bastholt L, Schmidt H, Bjerregaard JK, Herrstedt J, Svane IM. Age favoured overall survival in a large population-based Danish patient cohort treated with anti-PD1 immune checkpoint inhibitor for metastatic melanoma. Eur J Cancer (Oxford, England: 1990). 2019;119:122–31.

    Article  CAS  Google Scholar 

  39. Silva CC, Herchenhorn D. Treating the elderly with immune checkpoint inhibitors: real life experience from a large Brazilian center. J Clin Oncol. 2018;36:e15077–e1507715077.

    Article  Google Scholar 

  40. 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 

  41. 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;6:26.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Hurria A, Mohile S, Gajra A, et al. Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. J Clin Oncol. 2016;34:2366–71.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank BMS Medical Information and Alexander Connellan from Merck Sharp and Dohme for providing helpful information on nivolumab, pembrolizumab, and ipilimumab for the write up of this article.

Author information

Authors and Affiliations

  1. Adelaide Oncology and Haematology, Adelaide, SA, Australia

    Tiffany Foo & Rachel Roberts-Thomson

  2. Medical Oncology Department, Royal Adelaide Hospital, Adelaide, SA, Australia

    Gonzalo Tapia Rico

  3. Medical Oncology Department, The Queen Elizabeth Hospital, Adelaide, SA, Australia

    Rachel Roberts-Thomson

Authors
  1. Tiffany Foo
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  2. Gonzalo Tapia Rico
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  3. Rachel Roberts-Thomson
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Contributions

TF did the literature search and wrote up the manuscript. GTR and RR-T revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Gonzalo Tapia Rico.

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Funding

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

Conflict of interest

Dr. Rachel Roberts-Thomson has received honoraria from Bristol Myer Squibb and Merck, Sharpe and Dohme. Tiffany Foo and Gonzalo Tapia Rico declare that they have no conflicts of interest that might be relevant to the contents of this article.

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Foo, T., Tapia Rico, G. & Roberts-Thomson, R. Immunotherapy in Older Patients with Advanced Melanoma: A Review of the Current Evidence. Drugs Aging 37, 411–423 (2020). https://doi.org/10.1007/s40266-020-00762-1

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  • DOI: https://doi.org/10.1007/s40266-020-00762-1

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