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Safety and Effectiveness of Immune Checkpoint Inhibitors in Older Patients with Cancer: A Systematic Review of 48 Real-World Studies

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Abstract

Background

Over recent years, immune checkpoint inhibitors (ICIs) have changed the clinical management and prognosis for most cancers. However, data on older patients in clinical trials are scarce.

Objective

We performed a systematic review and pooled analysis of real-life studies to explore the efficacy and toxicity of ICIs in unselected older individuals in multiple tumor settings treated outside of clinical trials.

Patients and Methods

We searched articles, including prospective cohort studies, observational or retrospective series, or expanded access programs, published in English from 2010 to October 2020 in PubMed, MEDLINE, the Cochrane Library, and EMBASE. We excluded hematological malignancies.

Results

Forty-eight studies met the predefined criteria and were eligible for inclusion in the systematic review. We included 5524 patients. The pooled median overall survival was 8.9 (95% CI 7.3–10.5) and 14.3 (95% CI 11.3–17) months for non-small cell lung cancer (NSCLC: n = 17 studies; 95% in pretreated setting) and melanoma, respectively (n = 3). Median progression-free survival was 3.2 (95% CI 2.7–3.8) and 7.9 (95% CI 6.05–9.78) months for NSCLC and melanoma cohorts. Pooled rates of Grade 1–5 hepatitis, pneumonitis, hypothyroidism, and diarrhea were 5.3% (95% CI 3.7–7.6), 6% (95% CI 3.8–9.4), 8.3% (95% CI 5.4–12.5) and 7.6% (95% CI 5.7–10), respectively.

Conclusions

Our findings suggest that ICIs could be safely administered in older individuals with comparable survival outcomes with respect to younger individuals. Future studies should include some form of geriatric assessment to improve patient stratification.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30.

    Article  PubMed  Google Scholar 

  2. Sakakida T, Ishikawa T, Uchino J, et al. Safety and tolerability of PD-1/PD-L1 inhibitors in elderly and frail patients with advanced malignancies. Oncol Lett. 2020;20:14.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378:2078–92.

    CAS  PubMed  Google Scholar 

  4. Ahn BC, Pyo KH, Xin CF, et al. Comprehensive analysis of the characteristics and treatment outcomes of patients with non-small cell lung cancer treated with anti-PD-1 therapy in real-world practice. J Cancer Res Clin Oncol. 2019;145:1613–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Archibald WJ, Victor AI, Strawderman MS, et al. Immune checkpoint inhibitors in older adults with melanoma or cutaneous malignancies: The Wilmot Cancer Institute experience. J Geriatr Oncol. 2020;11:496–502.

    PubMed  Google Scholar 

  6. Baldini C, Martin Romano P, Voisin AL, et al. Impact of aging on immune-related adverse events generated by anti-programmed death (ligand)PD-(L)1 therapies. Eur J Cancer. 2020;129:71–9.

    CAS  PubMed  Google Scholar 

  7. Bastholt L, Schmidt H, Bjerregaard JK, et al. 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. 2019;119:122–31.

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  9. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Bjørnhart B, Hansen KH, Jørgensen TL, et al. Efficacy and safety of immune checkpoint inhibitors in a Danish real life non-small cell lung cancer population: a retrospective cohort study. Acta Oncol. 2019;58:953–61.

    PubMed  Google Scholar 

  11. Corbaux P, Maillet D, Boespflug A, et al. Older and younger patients treated with immune checkpoint inhibitors have similar outcomes in real-life setting. Eur J Cancer. 2019;121:192–201.

    CAS  PubMed  Google Scholar 

  12. Cowey CL, Liu FX, Boyd M, et al. Real-world treatment patterns and clinical outcomes among patients with advanced melanoma: a retrospective, community oncology-based cohort study (A STROBE-compliant article). Medicine (Baltimore). 2019;98:e16328.

    Google Scholar 

  13. Crinò L, Bidoli P, Delmonte A, et al. Italian Cohort of nivolumab expanded access program in squamous non-small cell lung cancer: results from a real-world population. Oncologist. 2019;24:e1165–71.

    PubMed  PubMed Central  Google Scholar 

  14. Cybulska-Stopa B, Ługowska I, Jagodzińska-Mucha P, et al. Immune checkpoint inhibitors therapy in older patients (≥ 70 years) with metastatic melanoma: a multicentre study. Postepy Dermatol Alergol. 2019;36:566–71.

    PubMed  PubMed Central  Google Scholar 

  15. De Giorgi U, Cartenì G, Giannarelli D, et al. Safety and efficacy of nivolumab for metastatic renal cell carcinoma: real-world results from an expanded access programme. BJU Int. 2019;123:98–105.

    PubMed  Google Scholar 

  16. Dudnik E, Moskovitz M, Daher S, et al. Effectiveness and safety of nivolumab in advanced non-small cell lung cancer: the real-life data. Lung Cancer. 2018;126:217–23.

    PubMed  Google Scholar 

  17. Elkrief A, Richard C, Malo J, et al. Efficacy of immune checkpoint inhibitors in older patients with non-small cell lung cancer: real-world data from multicentric cohorts in Canada and France. J Geriatr Oncol. 2020;11:802–6.

    PubMed  Google Scholar 

  18. Figueiredo A, Almeida MA, Almodovar MT, et al. Real-world data from the Portuguese Nivolumab Expanded Access Program (EAP) in previously treated non small cell lung cancer (NSCLC). Pulmonology. 2020;26:10–7.

    CAS  PubMed  Google Scholar 

  19. Finkelmeier F, Czauderna C, Perkhofer L, et al. Feasibility and safety of nivolumab in advanced hepatocellular carcinoma: real-life experience from three German centers. J Cancer Res Clin Oncol. 2019;145:253–9.

    CAS  PubMed  Google Scholar 

  20. Fox B, de Toro CM, Álvarez Álvarez R, et al. Efficacy and safety of immune checkpoint inhibitor immunotherapy in elderly cancer patients. Clin Transl Oncol. 2020;22:555–62.

    CAS  PubMed  Google Scholar 

  21. Fujimoto D, Yoshioka H, Kataoka Y, et al. Efficacy and safety of nivolumab in previously treated patients with non-small cell lung cancer: a multicenter retrospective cohort study. Lung Cancer. 2018;119:14–20.

    PubMed  Google Scholar 

  22. Galli G, De Toma A, Pagani F, et al. Efficacy and safety of immunotherapy in elderly patients with non-small cell lung cancer. Lung Cancer. 2019;137:38–42.

    PubMed  Google Scholar 

  23. Grossi F, Crinò L, Logroscino A, et al. Use of nivolumab in elderly patients with advanced squamous non-small-cell lung cancer: results from the Italian cohort of an expanded access programme. Eur J Cancer. 2018;100:126–34.

    CAS  PubMed  Google Scholar 

  24. Grossi F, Genova C, Crinò L, et al. Real-life results from the overall population and key subgroups within the Italian cohort of nivolumab expanded access program in non-squamous non-small cell lung cancer. Eur J Cancer. 2019;123:72–80.

    CAS  PubMed  Google Scholar 

  25. Hinata N, Yonese J, Masui S, et al. A multicenter retrospective study of nivolumab monotherapy in previously treated metastatic renal cell carcinoma patients: interim analysis of Japanese real-world data. Int J Clin Oncol. 2020;25:1533–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Joris S, Pieters T, Sibille A, et al. Real life safety and effectiveness of nivolumab in older patients with non-small cell lung cancer: results from the Belgian compassionate use program. J Geriatr Oncol. 2020;11:796–801.

    PubMed  Google Scholar 

  27. Juergens RA, Mariano C, Jolivet J, et al. Real-world benefit of nivolumab in a Canadian non-small-cell lung cancer cohort. Curr Oncol. 2018;25:384–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Khozin S, Carson KR, Zhi J, et al. Real-world outcomes of patients with metastatic non-small cell lung cancer treated with programmed cell death protein 1 inhibitors in the year following U.S. regulatory approval. Oncologist. 2019;24:648–56.

    CAS  PubMed  Google Scholar 

  29. Kobayashi K, Nakachi I, Naoki K, et al. Real-world efficacy and safety of nivolumab for advanced non-small-cell lung cancer: a retrospective multicenter analysis. Clin Lung Cancer. 2018;19:e349–58.

    CAS  PubMed  Google Scholar 

  30. Ksienski D, Wai ES, Croteau N, et al. Pembrolizumab for advanced nonsmall cell lung cancer: efficacy and safety in everyday clinical practice. Lung Cancer. 2019;133:110–6.

    PubMed  Google Scholar 

  31. Kubo T, Watanabe H, Ninomiya K, et al. Immune checkpoint inhibitor efficacy and safety in older non-small cell lung cancer patients. Jpn J Clin Oncol. 2020;50:1447–53.

    PubMed  Google Scholar 

  32. Lichtenstein MRL, Nipp RD, Muzikansky A, et al. Impact of age on outcomes with immunotherapy in patients with non-small cell lung cancer. J Thorac Oncol. 2019;14:547–52.

    CAS  PubMed  Google Scholar 

  33. Lim SM, Kim SW, Cho BC, et al. Real-world experience of nivolumab in non-small cell lung cancer in Korea. Cancer Res Treat. 2020;52:1112–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Liu FX, Ou W, Diede SJ, et al. Real-world experience with pembrolizumab in patients with advanced melanoma: a large retrospective observational study. Medicine (Baltimore). 2019;98:e16542.

    Google Scholar 

  35. Luciani A, Marra A, Toschi L, et al. Efficacy and safety of anti-PD-1 immunotherapy in patients aged ≥ 75 years with non-small-cell lung cancer (NSCLC): an Italian, multicenter, retrospective study. Clin Lung Cancer. 2020;21:e567–71.

    CAS  PubMed  Google Scholar 

  36. Merino Almazán M, Duarte Pérez JM, Marín Pozo JF, et al. A multicentre observational study of the effectiveness, safety and economic impact of nivolumab on non-small-cell lung cancer in real clinical practice. Int J Clin Pharm. 2019;41:272–9.

    PubMed  Google Scholar 

  37. Montana M, Garcia ME, Ausias N, et al. Efficacy and safety of nivolumab in patients with non-small cell lung cancer: a retrospective study in clinical practice. J Chemother. 2019;31:90–4.

    CAS  PubMed  Google Scholar 

  38. Muchnik E, Loh KP, Strawderman M, et al. Immune checkpoint inhibitors in real-world treatment of older adults with non-small cell lung cancer. J Am Geriatr Soc. 2019;67:905–12.

    PubMed  PubMed Central  Google Scholar 

  39. Nakamura Y, Miyazaki K, Aiko N, et al. Efficacy of PD-1 inhibitors in older non-small cell lung cancer patients. Anticancer Res. 2020;40:923–8.

    CAS  PubMed  Google Scholar 

  40. Okishio K, Morita R, Shimizu J, et al. Nivolumab treatment of elderly Japanese patients with non-small cell lung cancer: subanalysis of a real-world retrospective observational study (CA209-9CR). ESMO Open. 2020;5(4):e000656.

    PubMed  PubMed Central  Google Scholar 

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

    PubMed  Google Scholar 

  42. Ridolfi L, De Rosa F, Petracci E, et al. Anti-PD1 antibodies in patients aged ≥ 75 years with metastatic melanoma: a retrospective multicentre study. J Geriatr Oncol. 2020;11:515–22.

    PubMed  Google Scholar 

  43. Sabatier R, Nicolas E, Paciencia M, et al. Nivolumab in routine practice for older patients with advanced or metastatic non-small cell lung cancer. J Geriatr Oncol. 2018;9:494–500.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  45. Tamiya M, Tamiya A, Hosoya K, et al. Efficacy and safety of pembrolizumab as first-line therapy in advanced non-small cell lung cancer with at least 50% PD-L1 positivity: a multicenter retrospective cohort study (HOPE-001). Investig New Drugs. 2019;37:1266–73.

    CAS  Google Scholar 

  46. Tamura D, Jinnouchi N, Abe M, et al. Prognostic outcomes and safety in patients treated with pembrolizumab for advanced urothelial carcinoma: experience in real-world clinical practice. Int J Clin Oncol. 2020;25:899–905.

    CAS  PubMed  Google Scholar 

  47. Vitale MG, Scagliarini S, Galli L, et al. Efficacy and safety data in elderly patients with metastatic renal cell carcinoma included in the nivolumab Expanded Access Program (EAP) in Italy. PLoS ONE. 2018;13:e0199642.

    PubMed  PubMed Central  Google Scholar 

  48. Welaya K, Loh KP, Messing S, et al. Geriatric assessment and treatment outcomes in older adults with cancer receiving immune checkpoint inhibitors. J Geriatr Oncol. 2020;11:523–8.

    PubMed  Google Scholar 

  49. Yamaguchi O, Imai H, Minemura H, et al. Efficacy and safety of immune checkpoint inhibitor monotherapy in pretreated elderly patients with non-small cell lung cancer. Cancer Chemother Pharmacol. 2020;85:761–71.

    CAS  PubMed  Google Scholar 

  50. Youn B, Trikalinos NA, Mor V, et al. Real-world use and survival outcomes of immune checkpoint inhibitors in older adults with non-small cell lung cancer. Cancer. 2020;126:978–85.

    CAS  PubMed  Google Scholar 

  51. Landre T, Des Guetz G, Chouahnia K, et al. Immune checkpoint inhibitors for patients aged ≥ 75 years with advanced cancer in first- and second-line settings: a meta-analysis. Drugs Aging. 2020;37:747–54.

    CAS  PubMed  Google Scholar 

  52. van Holstein Y, Kapiteijn E, Bastiaannet E, et al. Efficacy and adverse events of immunotherapy with checkpoint inhibitors in older patients with cancer. Drugs Aging. 2019;36:927–38.

    PubMed  PubMed Central  Google Scholar 

  53. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Pawelec G. Immunosenescence and cancer. Biogerontology. 2017;18:717–21.

    CAS  PubMed  Google Scholar 

  56. Elias R, Karantanos T, Sira E, et al. Immunotherapy comes of age: immune aging & checkpoint inhibitors. J Geriatr Oncol. 2017;8:229–35.

    PubMed  Google Scholar 

  57. Pera A, Campos C, López N, et al. Immunosenescence: implications for response to infection and vaccination in older people. Maturitas. 2015;82:50–5.

    CAS  PubMed  Google Scholar 

  58. Wildiers H, Heeren P, Puts M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014;32:2595–603.

    PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Oncology Unit, Medical Sciences Department, ASST Bergamo Ovest, Piazzale Ospedale 1, 24047, Treviglio, BG, Italy

    Andrea Luciani & Fausto Petrelli

  2. Oncology Unit, Casa di cura Igea, Milan, Italy

    Antonio Ghidini

  3. Oncology Unit, ASST Bergamo Est, BG, Seriate, Italy

    Lorenzo Dottorini

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  1. Andrea Luciani
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  2. Antonio Ghidini
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  3. Lorenzo Dottorini
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  4. Fausto Petrelli
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Correspondence to Fausto Petrelli.

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Andrea Luciani, Antonio Ghidini, Lorenzo Dottorini, and Fausto Petrelli declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Luciani, A., Ghidini, A., Dottorini, L. et al. Safety and Effectiveness of Immune Checkpoint Inhibitors in Older Patients with Cancer: A Systematic Review of 48 Real-World Studies. Drugs Aging 38, 1055–1065 (2021). https://doi.org/10.1007/s40266-021-00899-7

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