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Efficacy of Immune-Checkpoint Inhibitors (ICI) in the Treatment of Older Adults with Metastatic Renal Cell Carcinoma (mRCC) – an International mRCC Database Consortium (IMDC) Analysis - Beyond the Abstract

Older adults with metastatic cancer are underrepresented in clinical trials in general.1 For trials involving immune-checkpoint inhibitors (ICI) in patients with metastatic renal cell carcinoma (mRCC) this also applies; older patients were underrepresented in the registration studies that led to the approval of ICI as standard of care treatment options (both for first-line and second-line). This is problematic as the external validity of such studies may be compromised.2 Older patients may not necessarily respond similarly to a younger population both in terms of efficacy and toxicity and therefore, effectiveness data of ICI specific to this important population is critical.

We leveraged the IMDC multinational consortium to interrogate whether the efficacy of ICIs is comparable between older adults (≥ 70 years at the time of treatment) and younger patients with mRCC.3 Effectiveness endpoints included: overall survival (OS), time to treatment failure (TTF), time to next treatment (TNT), and overall response rate (ORR). Hazard ratios were adjusted (aHR) for IMDC risk factors (performance status, time from diagnosis to treatment < 1 year, hemoglobin < lower limit of normal, neutrophils > upper limit of normal, platelets > upper limit of normal, corrected calcium > upper limit of normal), histology, line of treatment and older age.

We found that after multivariate adjustments, there were no differences in OS, TTF and TNT between older vs. younger patients with mRCC treated with ICIs. This is reassuring as ICIs are routinely being prescribed for older adults worldwide. IMDC congregates data from over 40 institutions including over 15 countries and represents clinical practice around the globe. Due to the retrospective nature of our work, we were not able to assess differences in toxicity profiles, which is also an important endpoint particularly when considering treatment with ICI combos. Nevertheless, there was no difference in TNT, which provides an indirect sense of differences in toxicity events – typically severe toxicity will lead to treatment discontinuation. It is reassuring that OS, TTF and TNT were non-significantly different amongst groups. Conversely, ORR was higher in youngers patients compared to older patients with mRCC. The reasons for this finding are obscure at this time and warrant further investigations/confirmations in other datasets.

In summary, we provide real-world evidence attesting that chronological age solely should not preclude prescription of ICI drugs to older patients with mRCC. Our work demonstrated that there was no statistical difference in OS, TTF and TNT between older vs. younger patients.


Written by: Daniel Vilarim Araujo, MD, Princess Margaret Cancer Centre & Shaan Dudani, MBChB, FRCPC, William Osler Health System 


References:

  1. Singh H, Kanapuru B, Smith C, et al: FDA analysis of enrollment of older adults in clinical trials for cancer drug registration: A 10-year experience by the U.S. Food and Drug Administration. Journal of Clinical Oncology 35:10009-10009, 2017
  2. Rothwell PM: Factors that can affect the external validity of randomised controlled trials. PLoS clinical trials 1:e9-e9, 2006
  3. Araujo DV, Wells JC, Hansen AR, et al: Efficacy of immune-checkpoint inhibitors (ICI) in the treatment of older adults with metastatic renal cell carcinoma (mRCC) – an International mRCC Database Consortium (IMDC) analysis. Journal of Geriatric Oncology


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