Efficacy and Adverse Events of Immunotherapy with Checkpoint Inhibitors in Older Patients with Cancer

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Abstract

The number of older patients with cancer is increasing as a result of the ageing of Western societies. Immune checkpoint inhibitors have improved cancer treatment and are associated with lower rates of treatment-related toxicity compared with chemotherapy in the general population. Nonetheless, immune checkpoint inhibitors have potentially serious immune-related adverse events, which might have a greater impact on older and more vulnerable patients and potentially influence treatment efficacy and quality of life. Previous clinical trials have shown no major increase in immune-related adverse events; however, older patients are underrepresented and relatively healthy in these trials. Observational studies suggest that older and more vulnerable patients may be at a higher risk of immune-related adverse events and early treatment discontinuation. Geriatric assessment could help identify older patients who will benefit from immune checkpoint inhibitors.

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Most cited references 29

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Ipilimumab is a human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4 and has shown promising activity in advanced melanoma. We aimed to ascertain the antitumour efficacy of ipilimumab in patients with advanced melanoma. We undertook a randomised, double-blind, phase 2 trial in 66 centres from 12 countries. 217 patients with previously treated stage III (unresectable) or stage IV melanoma were randomly assigned a fixed dose of ipilimumab of either 10 mg/kg (n=73), 3 mg/kg (n=72), or 0.3 mg/kg (n=72) every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. Randomisation was done with a permuted block procedure, stratified on the basis of type of previous treatment. The primary endpoint was best overall response rate (the proportion of patients with a complete or partial response, according to modified WHO criteria). Efficacy analyses were done by intention to treat, whereas safety analyses included patients who received at least one dose of ipilimumab. This study is registered with ClinicalTrials.gov, number NCT00289640. The best overall response rate was 11.1% (95% CI 4.9-20.7) for 10 mg/kg, 4.2% (0.9-11.7) for 3 mg/kg, and 0% (0.0-4.9) for 0.3 mg/kg (p=0.0015; trend test). Immune-related adverse events of any grade arose in 50 of 71, 46 of 71, and 19 of 72 patients at doses of 10 mg/kg, 3 mg/kg, and 0.3 mg/kg, respectively; the most common grade 3-4 adverse events were gastrointestinal immune-related events (11 in the 10 mg/kg group, two in the 3 mg/kg group, none in the 0.3 mg/kg group) and diarrhoea (ten in the 10 mg/kg group, one in the 3 mg/kg group, none in the 0.3 mg/kg group). Ipilimumab elicited a dose-dependent effect on efficacy and safety measures in pretreated patients with advanced melanoma, lending support to further studies at a dose of 10 mg/kg. Bristol-Myers Squibb. Copyright 2010 Elsevier Ltd. All rights reserved.

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Author and article information

Contributors

Nienke A. de Glas: N.A.de_Glas@lumc.nl

Journal

Journal ID (nlm-ta): Drugs Aging

Journal ID (iso-abbrev): Drugs Aging

Title: Drugs & Aging

Publisher: Springer International Publishing (Cham )

ISSN (Print): 1170-229X

ISSN (Electronic): 1179-1969

Publication date (Electronic): 18 July 2019

Publication date PMC-release: 18 July 2019

Publication date (Print): 2019

Volume: 36

Issue: 10

Pages: 927-938

Affiliations

[1 ]GRID grid.10419.3d, ISNI 0000000089452978, Department of Gerontology and Geriatrics, , Leiden University Medical Center, ; Leiden, The Netherlands

[2 ]GRID grid.10419.3d, ISNI 0000000089452978, Department of Medical Oncology, , Leiden University Medical Center, ; PO Box 9600, 2300 RC Leiden, The Netherlands

[3 ]GRID grid.10419.3d, ISNI 0000000089452978, Department of Surgery, , Leiden University Medical Center, ; Leiden, The Netherlands

[4 ]GRID grid.7692.a, ISNI 0000000090126352, Department of Geriatrics, , Utrecht University Medical Center, ; Leiden, The Netherlands

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Yara van Holstein http://orcid.org/0000-0002-6882-639X

Article

Publisher ID: 697

DOI: 10.1007/s40266-019-00697-2

PMC ID: 6764930

PubMed ID: 31317421

SO-VID: a9f2f76c-62e0-4101-9020-c30be60225c2

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Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Efficacy and Adverse Events of Immunotherapy with Checkpoint Inhibitors in Older Patients with Cancer

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Most cited references 29

Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study.

Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.

Dose-related patterns of glucocorticoid-induced side effects.

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