The medical treatment of metastatic renal cell cancer in the elderly: Position paper of a SIOG Taskforce
Section snippets
Conclusions and recommendations
On the limited information available, which comes mostly from retrospective analysis of subgroups in controlled and uncontrolled clinical trials, it would appear that patients aged over 65 years benefit as much from targeted therapies as younger patients and do not experience more frequent or severe toxicity. However, no data are available for patients aged over 85 years.
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It is accepted that analysing clinical trial data by age alone provides only limited guidance since eligibility criteria
Expanding range of agents effective in mRCC
For several decades, the systemic management of metastatic renal cell cancer (mRCC) was confined to the use of interferon (IFN) and interleukin-2 (IL-2). Both agents can achieve responses; and, in the case of IL-2, these are durable in a small proportion of patients [5]. However, benefit appears confined to patients with limited disease and good performance status. For the majority, especially those elderly patients who are less fit, the toxicities of cytokine therapy have proved a major
Age of patients included in recent pivotal trials
None of the fully published phase III trials listed in Table 2 had an upper age limit to recruitment. This itself is of interest, since a maximum age would generally have been stipulated in similar studies carried out a decade ago. Across these studies and their treatment arms, the average age of patients entered was remarkably similar (the lowest median being 58 years in the sorafenib arm of the placebo-controlled phase III, and the highest a median of 62 years, in the sunitinib arm of the
Phase III data
In the pivotal ph III comparison against IFN in the first-line setting, all patients had an ECOG performance status of 0 or 1, and the great majority had good or intermediate-risk disease according to the MSKCC prognostic index [8]. Overall, treatment with sunitinib was associated with a highly significant benefit in PFS (median 11 months, compared with 5 months in patients randomised to IFN; corresponding to an HR of 0.42). Importantly in the present context, the HR in the 275 patients aged 65
Discussion
In the field of oncology as a whole, elderly patients are at risk of receiving sub-optimal therapy. In part, this may reflect patients’ preference to avoid aggressive interventions. However, it may also reflect the bias of clinicians, or the lack of relevant clinical data and management guidelines. As far as we know, this paper represents the first systematic review of the role of targeted agents specifically in the elderly population.
Recent pivotal trials in mRCC (at least, those that are
Conflict of interest statements
JB has been a consultant or advisor to Pfizer, Bayer and Roche and has received research funding from Pfizer.
SN was a consultant for Pfizer, Wyeth and Roche and has received honoraria from Pfizer, Wyeth and Bayer.
BE has to disclose honorarium from the following drug companies: Bayer, Roche, Wyeth, Novartis, Pfizer, Inate Pharma, Antigenics.
AA has been an advisor to Bayer and Wyeth.
MA is consultant to Merck, Pfizer, Roche and Bayer/Schering.
Acknowledgements
We acknowledge and thank Prof. UE Studer (Bern), Prof. P Mulders (Nijmegen) and Prof. B Ljungberg (Umea) for their constructive comments when reviewing this paper. Rob Stepney, medical writer, drafted the manuscript.
An unrestricted grant to SIOG was given by Wyeth Europe Ltd.
Dr. Joaquim Bellmunt is Assistant Professor of Medicine at the Universitat Pompeu Fabra (UPF) in Barcelona and Chief of the Solid Tumor Oncology Section at the Medical Oncology Service of Hospital del Mar. He is President and Co-founder of the Spanish Oncology Genitourinary Group. He is also a Consultant for the EORTC – GU Group, Chairman of the group’s Advanced Bladder Committee and Coordinator of the Intergroup study in advanced transitional Cancer (EORTC 30987) and EORTC study 30986 in unfit
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Representation of older patients in the safety analysis of protein kinase inhibitor registration studies
2023, Journal of Geriatric OncologyComprehensive geriatric assessment is an independent prognostic factor in older patients with metastatic renal cell cancer treated with first-line Sunitinib or Pazopanib: a single center experience
2021, Journal of Geriatric OncologyCitation Excerpt :In the phase III, double-blinded, cross-over PISCES trial about 70% of the enrolled subjects (median age: 63 years) preferred Pazopanib to Sunitinib in terms of tolerability (p < 0.001) [7]. According to subgroup analyses, the activity of TKIs in the older adults (defined as older than 65 years) was found to be not inferior to that obtained in younger patients with metastatic RCC in terms of PFS and OS [8] [9], but toxicities may be relevant and severely impact on patients' independence in daily activities and on her/his quality of life [8]. Thus, dose reductions, alternative schedules or treatment suspensions are crucial in order to improve tolerability and increase treatment compliance to Sunitinib or Pazopanib, as showed in many retrospective analyses [10] [11] [12] [13].
SIOG guidelines- essential for good clinical practice in geriatric oncology
2019, Journal of Geriatric OncologyElderly patients with metastatic renal cell carcinoma: position paper from the International Society of Geriatric Oncology
2018, The Lancet OncologyCitation Excerpt :Now, overall survival is 24–30 months.3 A systematic review4 published in 2009 by a task force from the International Society of Geriatric Oncology suggested that the survival benefits in patients aged 65 years and older were similar to those in younger patients, and that the frequency and severity of major toxic effects did not differ according to age. However, the authors of that systematic review4 acknowledged the absence of trials that had been specifically done in elderly patients, and that the conclusions drawn from retrospective subgroup analyses by age must be treated with caution, because of smaller sample sizes and other biases affecting the analyses.
Dr. Joaquim Bellmunt is Assistant Professor of Medicine at the Universitat Pompeu Fabra (UPF) in Barcelona and Chief of the Solid Tumor Oncology Section at the Medical Oncology Service of Hospital del Mar. He is President and Co-founder of the Spanish Oncology Genitourinary Group. He is also a Consultant for the EORTC – GU Group, Chairman of the group’s Advanced Bladder Committee and Coordinator of the Intergroup study in advanced transitional Cancer (EORTC 30987) and EORTC study 30986 in unfit patients. His research interests include new drugs, translational and early clinical research in the area of growth factor receptors and downstream molecules as targets for cancer therapy. Dr. Bellmunt has published over 70 peer-reviewed articles and over 100 abstracts and book chapters.