Adjuvant therapy landscape for renal cell carcinoma continues to evolve
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For years, adjuvant therapy for renal cell carcinoma was ‘under future direction’ in any research discussion.
This is not the case anymore, according to a speaker at Chemotherapy Foundation Symposium.
“Twenty-nine years ago, one of the first adjuvant cytokine randomized studies was presented at the ASCO Annual meeting in which researchers found no difference in outcomes whether patients with renal cell carcinoma received cytokine therapy or not. Since this trial, all cytokine studies have been negative no matter the primary endpoint — OS, DFS or recurrence,” Toni K. Choueiri, MD, director of Lank Center for Genitourinary Oncology and the Kidney Cancer Center at Dana-Farber Cancer Institute, and Jerome and Nancy Kohlberg chair and professor of medicine at Harvard Medical School, said during a presentation.
Then, during the mid-2000s, tyrosine kinase inhibitors came into the mix.
“These agents mostly targeted VEGF or mTOR,” Choueiri said. “The most recent study on an mTOR inhibitor is still ongoing but, out of the other five established studies, essentially four were negative. The one study that was positive, S-TRAC, reported positive DFS with adjuvant sunitinib [Sutent, Pfizer] vs. placebo in patients with high-risk renal cell carcinoma. One important aspect of this study is that treatment discontinuation occurred in 28% of patients assigned sunitinib, and there was a reduced health-related quality of life.”
In the 2017 ASSURE trial, researchers assessed sorafenib (Nexavar, Bayer) vs. sunitinib vs. placebo among patients with high-risk renal cell carcinoma.
“This study was also negative and is another reason why the use of sunitinib has not picked up, even though it is approved,” Choueiri said.
In the randomized, double-blind, international KEYNOTE-564 trial, researchers examined the use of pembrolizumab (Keytruda, Merck) or placebo for patients with high-risk, fully resected renal cell carcinoma.
“We struggled with finding patients at increased risk for disease progression for this trial,” Choueiri said. “The study met its primary endpoint of DFS, showing a decrease of 32% in the risk for recurrence or death. Of note, follow-up remains short at only 24 months.”
The question now is whether pembrolizumab is ready for the clinic once FDA-approved, Choueiri said.
“On one hand, there is an early separation of curves, less toxicity compared with sunitinib and a trend for OS after 25% of OS events,” he said. “However, we all know that independent of what solid tumor we are treating, we are always overtreating when surgery alone could be curative. In addition, there are some folks who would like to see this agent compared with sunitinib and want to wait for OS results.”
Additional data will be published on KEYNOTE-564, Choueiri added.
“OS will be updated and there will be data on tissue and blood-based biomarkers There are still many unanswered questions with this trial design.”
References:
Choueiri TK. Adjuvant therapy for RCC: Is it finally here? Presented at: 39th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow; Nov. 3-5, 2021.
Choueiri TK, et al. Abstract LBA5. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.
Haas NB, et al. JAMA Oncol. 2017; doi:10.1001/jamaoncol.2017.0076.
Ravaud A, et al. Abstract LBA11_PR. Presented at: European Society for Medical Oncology Congress; Oct. 7-11, 2016; Copenhagen, Denmark.
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Choueiri TK. Adjuvant therapy for RCC: Is it finally here? Presented at: 39th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow; Nov. 3-5, 2021.
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