CheckMate-214: Combination therapy is the new ‘standard of care’ in RCC
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The release of findings from the Checkmate-214 study produced multiple changes for specialists in renal cell carcinoma.
Chung-Han Lee, MD, PhD, medical oncologist at Memorial Sloan Kettering Cancer Center, spoke with Healio about CheckMate-214 findings, clinical relevance, FDA approvals of TKI/IO regimens and possible novel agents.
How has the prognosis for patients labeled intermediate and poor outlook changed since the CheckMate-214 findings were released?
CheckMate-214 was a randomized phase 3 clinical trial that investigated the combination immunotherapy with ipilimumab (Yervoy, Bristol-Myers Squibb) and nivolumab (Opdivo, Bristol-Myers Squibb) vs. sunitinib (Sutent, Pfizer) in the first-line setting. The study demonstrated improved objective response rate and also improved overall survival in patients with advanced or metastatic renal cell carcinoma. This study lead to the regulatory approval of this combination and has rapidly become a new standard of care for patients with RCC. Since the initial release of data, there have been multiple updates and most recently we have seen the results of the extended follow up. It has been very exciting to see that some patients are able to obtain durable responses to the combination of ipilimumab/nivolumab.
How has the new standard of care changed since the CheckMate-214 trial?
Since the release of CheckMate-214, multiple new regimens have obtained regulatory approval in the United States for advanced and metastatic RCC. Broadly speaking, they can be grouped into two different approaches: combination immunotherapy with ipilimumab/nivolumab vs. combination VEGF targeted and IO therapy with combinations such as axitinib (Inlyta, Pfizer) with pembrolizumab (Keytruda, Merck) and axitinib (Inlyta, Pfizer) with avelumab (Bavencio; EMD Serono, Pfizer).
What data from these findings prompted changes in your practice?
Very exciting from this data have been the improvements in clinical responses for patients with intermediate and poor risk disease and the percentage of patients who have long-term responses to treatment. Based on the current data, we have largely replaced single agent TKI for patients with intermediate and poor risk disease.
What new combinations are available or under study for patients with RCC?
Since the results for CheckMate-214 were first released, we have seen the FDA approval of two TKI/IO regimens axitinib/avelumab and axitinib/pembrolizumab. We have also seen a positive press release for the phase 3 trial of cabozantinib (Cabometyx, Ipsen) plus nivolumab; however, at this time, the data from that study has not yet been released. For example, with the phase 3 IMmotion151 trial assessing bevacizumab (Avastin, Genentech) and atezolizumab (Tecentriq, Genentech), the manufacturer issued a press release indicating the primary endpoint was met. We do not know the nuances of the results yet, but the trial was declared positive.
Other trials that are particularly interesting include evaluation of lenvatinib (Lenvima, Eisai) plus pembrolizumab in the first-line setting. This combination has seen encouraging results after patients have progressed on VEGF-targeted therapy and after patients have progressed on PD-1 immunotherapy. These is also an ongoing clinical trial of cabozantinib/ipi/nivo vs. ipi/nivo.
What biomarkers have become available for use since the CheckMate-214 trial?
To date, biomarkers for RCC remain a work in progress. Much of the decision regarding treatment choice is based on clinical or histologic parameters. There are encouraging results from expression profiling and genomic analysis; however, these are not yet ready for clinical practice.
What else is in the pipeline to RCC treatment?
There is also considerable interest in development of novel agents which target other pathways. Right now, there is interest in seeing the response to metabolic inhibition with the glutaminase inhibitor telaglenastat and also the HIF2A inhibitor.
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