Michael A. Carducci, MD, who is a professor of oncology and urology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, said this study is limited because it is a database study and it also looked at patients who were treated before newer and more effective targeted therapies became available. “It is outdated in terms of current practice. We know that advances have occurred in renal cancer therapy and there has been a sea change in outcomes from patients treated before 2007. Immunotherapy is now an important option,” Dr Carducci told Cancer Therapy Advisor.

Pavlos Msaouel. MD, PHD, who is an assistant professor in the department of genitourinary medical oncology at The University of Texas MD Anderson Cancer Center, Houston, said this study is interesting because it provides a snapshot of Medicare patients from across the United States. “Any causal inferences will, of course, always be limited by the retrospective and nonrandomized nature of the study. But the main limitation of the study is that it uses data from 2000 to 2013. Since 2015, immune checkpoint inhibitors such as nivolumab and ipilimumab, alone or in combination, have been a whole new therapeutic class approved for the treatment of clear cell renal cell carcinoma. In addition, newer targeted agents such as cabozantinib were not available during the time period of the trial,” said Dr Msaouel.

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He said recently the US Food and Drug Administration has approved combinations of immune checkpoint inhibitors with targeted therapies (pembrolizumab plus axitinib or avelumab plus axitinib) and these combination therapies have completely changed the therapeutic landscape of clear cell RCC. “Observational data from large databases such as SEER are certainly valuable, but given the rapidly evolving treatment landscape in renal cell carcinoma, we would need much more up-to-date data than this study provides. Our therapeutic armamentarium now includes multiple newer agents that are usually more tolerable for patients aged 65 years and older,” Dr Msaouel told Cancer Therapy Advisor.


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Benjamin Maughan MD, PharmD, who is an assistant professor of genitourinary medical oncology, division of oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, said this is study is beneficial because it highlights the value of treatment in older patients with metastatic RCC. However, it looked at patients receiving sunitinib and sorafenib or the mTOR inhibitors everolimus and temsirolimus as opposed to more frequently used TKIs today, such as cabozantinib and axitinib. “The modern practice only rarely uses mTOR therapy and never uses the nontargeted therapies evaluated in this study. The nontargeted therapies used today include checkpoint inhibitors, such as pembrolizumab, avelumab, nivolumab, and ipilimumab,” Dr Maughan added.

He said clinical trials have recently demonstrated that the modern TKIs are much more potent than those used in the current study and tolerability is not an issue. “The authors suggest that there is less benefit from TKI therapy in the real-world population they studied compared to the clinical trials. This is difficult to justify based on their results given the short median follow-up of only approximately 8 months,” Dr Maughan told Cancer Therapy Advisor.

He said newer therapies that now are available, such as pazopanib, axinitib, and lenvatinib, can be very well tolerated even in a more frail population and provide meaningful clinical benefit, such as palliation of cancer-related symptoms and prolongation of survival. “I think that in most situations, patients should be offered monotherapy [tyrosine kinase inhibitor] treatment at a minimum.

The outlook for patients who are older and/or have significant comorbidities continues to improve. In 2019, additional clinical trials reported on newer immunotherapy combination that substantially improve clinical outcomes compared with single-agent tyrosine kinase inhibitor therapy and are still very well tolerated,” said Dr Maughan. “I think the argument of not treating patients due to potential for side effects is no longer a tenable position for most patients.”

Reference

Li P, Jahnke J, Pettit AR, et al. Comparative survival associated with use of targeted vs nontargeted therapy in Medicare patients with metastatic renal cell carcinoma. JAMA Netw Open. 2019;2(6):e195806.