Phase III data point to new standard of care for mRCC

Sunitinib (SUTENT) alone was not inferior to nephrectomy followed by sunitinib in patients with intermediate- or poor-risk metastatic renal cell carcinoma (RCC), interim results of the randomized, 450-patient phase III CARMENA trial showed.

Median overall survival was 18.4 months for patients who received sunitinib alone, versus 13.9 months for patients who underwent nephrectomy followed by sunitinib in this study.

The hazard ratio for death was 0.89, with the upper boundary of the 95% confidence interval not exceeding the non-inferiority limit (95% CI, 0.71-1.10), according to results presented at the American Society of Clinical Oncology annual meeting in Chicago.

“We propose that when medical treatment is required, cytoreductive nephrectomy should no longer be considered the standard of care for these patients with synchronous, metastatic RCC,” investigator Arnaud Méjean, MD, PhD, of Hôpital Europeén Georges-Pompidou – Paris Descartes University, France, said at an ASCO press conference.

While the numerical difference in median survival suggests sunitinib alone may have a greater benefit, that can’t be concluded since this was a non-inferiority trial, according to Dr. Méjean.

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This study presented Dr. Méjean has “firmly demonstrated” that in the context of the targeted therapy sunitinib, there doesn’t seem to be a need to remove the kidney in patients with advanced and metastatic disease, according to ASCO expert Sumanta K. Pal, MD.

“He’s really flipped the existing paradigm that we have in the management of advanced kidney cancer in this regard,” Dr. Pal said.

The clinical practice of cytoreductive nephrectomy in these patients has been based on retrospective studies of national data repositories and data banks suggesting a benefit.

“Admittedly, this isn’t based on a very high level of evidence,” said Dr. Pal. “The highest bar is what Dr. Méjean has presented, and that’s a randomized, prospective clinical trial.”

However, the role of cytoreductive nephrectomy may need to be reassessed in light of expanding treatment options for advanced RCC. The multikinase inhibitor cabozantinib (CABOMETYX) was approved by the FDA in January of this year, while nivolumab (Opdivo) and ipilimumab (Yervoy), a dual immunotherapy regimen, was approved in April.

“In the context of these newer therapies, I think we may have to go back to the drawing board once again and assess the relevance of removing the primary tumor,” said Dr. Pal.

The CARMENA trial enrolled a total of 450 patients with synchronous metastatic RCC classified as having MSKCC intermediate-risk or poor-risk disease. They were randomized 1:1 to receive standard therapy, consisting of nephrectomy followed by sunitinib initiated 3 to 6 weeks after the procedure; or to an experimental arm of sunitinib alone.

Sunitinib was given at a 50-mg daily dose in cycles of 28 days on, 14 days off, every 6 weeks.

The results were published concurrently in the New England Journal of Medicine (June 3, 2018 [epub ahead of print]).

Next:Drs. Motzer, Russo discuss study in editorialIn an editorial accompanying the study report, Robert J. Motzer, MD, and Paul Russo, MD, said nephrectomy “remains an essential component of care” in properly chosen patients with metastatic RCC (NEJM June 3, 2018 [epub ahead of print]).

“For practicing surgeons and medical oncologists, these data should not lead to the abandonment of nephrectomy, but instead emphasize the importance of careful selection of patients undergoing nephrectomy, on the basis of published risk models,” Drs. Motzer and Russo wrote.

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Nephrectomy for stage IV disease removes the potential for bleeding and pain during subsequent systemic therapy, and by removing the primary tumor, may eliminate a potential source of immunosuppressive or tumor-promoting growth factors, they said in the editorial.

For disclosures related to CARMENA, click here. For disclosures related to Dr. Motzer and Dr. Russo’s editorial, click here.