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Drake Discusses CARMENA Trial and Emerging Approaches in RCC

Jason Harris
Published: Thursday, Jul 12, 2018

Charles Drake, MD, PhD
Charles Drake, MD, PhD
Sunitinib (Sutent) alone was noninferior for median overall survival (OS) compared with sunitinib plus cytoreductive nephrectomy in patients with synchronous metastatic renal cell carcinoma (mRCC), according to findings from the phase III noninferiority CARMENA trial presented at the 2018 ASCO Annual Meeting.

In CARMENA, the median OS was 18.4 months for patients in the sunitinib arm compared with 13.9 months for the surgery arm (HR, 0.89; 95% CI, 0.71-1.10). The prespecified noninferiority margin was ≤1.20 for the upper bound of the confidence interval.

Sunitinib produced similar median OS results for patients with intermediate (23.4 vs 19.0 months; HR, 0.92; 95% CI, 0.68-1.24) and poor prognosis (13.3 vs 10.2 months; HR, 0.85; 95% CI, 0.62-1.17). Patients with good prognosis were not eligible for enrollment.

In an interview with OncLive, Charles G. Drake, MD, PhD, director of Genitourinary Oncology at New York-Presbyterian/Columbia University Medical Center and co-director of Columbia’s Cancer Immunotherapy Programs, discussed the importance of the CARMENA results, the future of cytoreductive nephrectomy, and how the use of immunotherapy could change treatment in this setting.

OncLive: What was the rationale for the study?

Drake: We really don't know, when a patient presents with metastatic kidney cancer, whether taking out the primary kidney lesion will help them live longer or better. There are a number of retrospective studies, but all of them are subject to bias because the surgeon picks the person who is healthy enough to have their kidney removed.

This was a very good trial. This was a randomized trial where patients with intermediate- and high-risk kidney cancer were randomized to have either surgery followed by standard therapy or to have standard therapy alone.

Patients were identified—and, this is important—by urologists. The urologist would say, “This is a pretty good patient. They have metastatic kidney cancer. They're eligible for a trial where they would either have their tumor resected or not resected.”

What were the results?

The results were surprising. The patients who had their primary tumor taken out did not live longer. The 2 approaches were statistically equivalent in terms of overall survival.

What is the current role of cytoreductive nephrectomy?

Up until this study, it was reasonably well used. There were 2 older studies that performed the experiment before we had tyrosine kinase inhibitors (TKIs). Those studies compared surgery plus interferon to interferon alone. Those older studies were positive. Based on that, there was widespread use of nephrectomy.

However, there is always the question in the modern era that, when [CARMENA] was started, whether this would look the same with a TKI—sunitinib, actually—and it didn't. The study was not positive; it didn't suggest a benefit from the surgery.

What is the significance of these results as far as the ongoing use of cytoreductive nephrectomy?

It's very interesting. You would think that having a randomized phase III study would change practice worldwide and it will generally reduce the use of cytoreductive nephrectomy. Nevertheless, there is always the question of patient selection, and there are certain to be some individuals who believe they can select patients who would benefit from cytoreductive nephrectomy. It's not going to go away. There will be some cytoreductive nephrectomy performed, probably in healthier patients, which are better surgical candidates. I do think, overall, global use will go down.

Have investigators explored the use of immunotherapy in this setting?

Sunitinib is a standard first-line treatment for kidney cancer, but it's becoming decreasingly used in the first-line setting. For these intermediate- and high-risk patients, right now, it's probably not the standard of care. The standard of care at Columbia University Medical Center and other medical centers, especially academic centers, is combination immunotherapy with anti–PD-1 and anti–CTLA-4. Whether you would get the same result with moderate immunotherapy or not is a very good question.

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