NEW YORK — Most clinical trials provide limited guidance on the appropriate treatment of patients seen in clinical practice. Particularly in oncology, participants in trials tend to be significantly younger and in substantially better health than the average patient. Renal cell carcinoma (RCC) provides a clear example of the challenge.
In the United States, the average age at diagnosis of RCC is 64, with most people diagnosed between the ages of 65 and 74 and a significant increase in incidence in those between the ages of 75 and 89. “Multiple regimens incorporating tyrosine kinase inhibitors (TKI) or immune checkpoint inhibitors (ICI), either alone or in combination, confer a significant [overall survival] benefit in 1L metastatic clear cell RCC,” said researchers at the American Society of Clinical Oncology annual meeting in June. “However, guidance for optimal treatment selection in elderly patients remains limited.”
For clinicians at the VA, determining the optimal treatment for elderly patients with RCC is critical. The majority of veterans receiving care through the VA are male, and RCC is twice as common in men as in women. VA patients also tend to be elderly, like the bulk of RCC patients, and are more likely to be or have been smokers, a known risk factor for the malignancy.
To better understand which treatments worked best in the population most clinicians will encounter, researchers at the Icahn School of Medicine at Mount Sinai conducted a network meta-analysis that compared the efficacy of several first-line treatments for elderly patients with advanced RCC. More than one-third of patients with RCC have stage III or IV cancer at the time of diagnosis.
The researchers performed a database search for randomized controlled trials of first-line regimens in patients at least 65 years of age with advanced RCC. They identified 14 trials that included more than 2,100 patients in total, and five studies with a combined 1,529 patients that had progression-free and overall survival data available for analysis.1
The team found that pembrolizumab plus axitinib provided significantly improved overall survival compared to sunitinib (HR 0.68, 95% CI 0.48-0.97), as did pembrolizumab plus lenvatinib (HR 0.61, 95% CI 0.4-0.94). They observed no statistically significant difference in overall survival between TKI/ICI combinations (pembrolizumab plus lenvatinib, pembrolizumab plus axitinib, avelumab plus axitinib, and nivolumab plus cabozantinib) and dual ICI regimens (nivolumab plus ipilimumab).
On the other hand, pembrolizumab plus lenvatinib, nivolumab plus cabozantinib, pembrolizumab plus axitinib, and cabozantinib monotherapy all demonstrated better progression-free survival than sunitinib. Pembrolizumab plus lenvatinib provided a significant advantage in progression-free survival compared to pembrolizumab plus axitinib (HR 0.58, 95% CI 0.37-0.91). Pembrolizumab plus lenvatinib provided no statistically significant difference in progression-free survival compared to nivolumab plus cabozantinib or cabozantinib monotherapy.
Overall, currently recommended TKI/ICI combinations and dual ICI regimens provided similar overall survival benefits compared to sunitinib. TKI/ICI combinations (with the exception of pembrolizumab plus axitinib) and cabozantinib monotherapy also provided similar progression-free survival benefits compared to sunitinib.
- Fujiwara Y, Miyashita H, Liaw BCH. First-line therapy for elderly patients with advanced renal cell carcinoma (aRCC): A systemic review and network meta-analysis. J Clin Oncol. 2022;40 (suppl 16; abstr 4532).
