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Immune Checkpoint Inhibitors for Patients Aged ≥ 75 Years with Advanced Cancer in First- and Second-Line Settings: A Meta-Analysis

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Abstract

Background

The impact of aging on the effectiveness of immune checkpoint inhibitors (ICIs) remains controversial, and little is known on the subject in adults aged ≥ 75 years.

Objective

The objective of this comprehensive meta-analysis was to assess the efficacy of ICIs in patients aged ≥ 75 years.

Methods

We performed a meta-analysis of published randomized controlled trials concerning ICIs (as monotherapy or in combination) versus standard therapy in patients with advanced solid tumors between January 2010 and January 2020. We compared overall survival between older (aged ≥ 75 years) and younger (< 75 years) patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were collected and pooled. The secondary endpoint focused on the impact of the use of ICIs in first- and second-line settings.

Results

In total, 15 phase III studies evaluating anti-programmed cell death 1 (anti-PD-1) (nivolumab or pembrolizumab), anti-programmed cell death ligand 1 (anti-PD-L1) (atezolizumab or avelumab), or anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA-4) (ipilimumab) therapies were included. Enrolled patients had non-small-cell lung cancer, renal cell carcinoma, melanoma, head and neck squamous cell carcinoma, or gastric cancer. Eight studies assessed treatment in the first-line setting and seven in the second-line setting. The median age was 64 years, with 906 patients aged ≥ 75 years (552 in first line, 354 in second line) and 8741 were aged < 75 years (4992 in first line, 3749 in second line). In the first-line setting, HRs for death were 0.78 (95% CI 0.61–0.99) in patients aged ≥ 75 years versus 0.84 (95% CI 0.71–1.00) in those aged < 75 years. In the second-line setting, HRs for death were 1.02 (95% CI 0.77–1.36) in patients aged ≥ 75 years versus 0.68 (95% CI 0.61–0.75) in those aged < 75 years, with a statistically significant difference observed between subgroups (p = 0.009 for interaction).

Conclusions

ICIs appear to be effective in patients aged ≥ 75 years. However, the survival benefit is mainly observed in first-line treatment and remains unclear in the second-line setting.

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Author information

Authors and Affiliations

  1. Geriatric Oncology Coordination Unit, UCOG 93, APHP, HUPSSD, Université Sorbonne Paris Nord, Sevran, France

    Thierry Landre

  2. Oncology Department, CH Delafontaine, Université de Limoges, St Denis, France

    Gaetan Des Guetz

  3. Oncology Department, APHP, Avicenne, HUPSSD, Université Sorbonne Paris Nord, Bobigny, France

    Kader Chouahnia

  4. Geriatric Department, UCOG Paris Nord, AP-HP, Bretonneau Hospital, 23 Rue Joseph de Maistre, 75018, Paris, France

    Virginie Fossey-Diaz

  5. Department of Medical Oncology, UCOG Paris Nord, AP-HP, Saint-Louis Hospital, 1 Avenue Claude Vellefaux, 75010, Paris, France

    Stéphane Culine

  6. Paris Diderot University, 5 Rue Thomas Mann, 75013, Paris, France

    Stéphane Culine

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  1. Thierry Landre
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Contributions

TL, SC, and GDG designed the research, collected the data, analyzed and interpreted the data, and wrote the manuscript. SC and GDG contributed to the collection of data and revision of the manuscript. KC and VFD participated in the elaboration of the research design and revision of the manuscript.

Corresponding author

Correspondence to Thierry Landre.

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Funding

No sources of funding were used to conduct this study or prepare this manuscript.

Conflict of interest

TL, GDG, KC, VFD, and SC have no conflicts of interest that might be relevant to the contents of this article.

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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 37, 747–754 (2020). https://doi.org/10.1007/s40266-020-00788-5

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  • DOI: https://doi.org/10.1007/s40266-020-00788-5

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