Carmena Trial: Should Nephrectomy Be Standard for Metastatic RCC?

June 10, 2019

In this randomized phase III trial, researchers compared cytoreductive nephrectomy vs sunitinib alone in patients with metastatic renal cell carcinoma.

Cytoreductive nephrectomy for metastatic renal cell carcinoma (RCC) is not superior to treatment with sunitinib alone, and may only have benefit in a very select group of patients, according to updated results from the Carmena trial (abstract 4508) presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.

The only subgroup showing a benefit with nephrectomy plus sunitinib was intermediate-risk patients with only one risk factor who had a median overall survival of 31.4 months with a combined approach compared with 25.2 months with sunitinib alone (hazard ratio [HR], 1.29; 95% CI, 0.85–1.98; P = .232), according to study presenter Arnaud Mejean, MD, PhD, of Hôpital Européen Georges-Pompidou and Paris Descartes University.

“It confirms the cytoreductive nephrectomy should no longer be considered the standard of care for patients with metastatic RCC,” said Mejean. “However, this new analysis suggests that cytoreductive nephrectomy might be beneficial for patients with only one IMDC [International Metastatic RCC Database Consortium] risk factor and that the number of metastatic sites per se is not helpful to define good candidates for surgery.”

Carmena was a randomized phase III trial comparing nephrectomy followed by sunitinib compared with sunitinib alone with stratification of patients by Memorial Sloan-Kettering Cancer Center (MSKCC) risk groups. Based on the initial analysis of these results, cytoreductive nephrectomy was no longer recommended in metastatic RCC.

These updated results looked at different risk subgroups form the Carmena trial. For the purpose of this analysis, patients were re-classified by IMDC risk groups, and analyzed by presence of one or more risk factor and metastatic site.

The updated median follow-up was 61.5 months. Using the IMDC risk groups, 58.6% of patients were intermediate risk and 41.4% were poor risk.

In the intention-to-treat group, the median overall survival for nephrectomy plus sunitinib was 15.6 months compared with 19.8 months for sunitinib alone (HR, 0.97; 95% CI, 0.79–1.19).

Nephrectomy plus sunitinib was not superior to sunitinib alone in the majority of subgroups. Among all patients with intermediate risk, the median overall survival was 19.0 months for nephrectomy plus sunitinib compared with 27.9 months for sunitinib alone (HR, 0.95; 95% CI, 0.70–1.24).

In those patients with intermediate-risk and two risk factors, the median overall survival was 17.6 months for the combined approach compared with 31.2 months for sunitinib alone (HR, 0.63; 95% CI, 0.44–0.97; P = .033).

Nephrectomy plus sunitinib was not superior to sunitinib alone for patients with one metastatic site, or those with more than one metastatic site.

In addition, patients assigned to sunitinib alone who then underwent secondary nephrectomy had a median overall survival of 48.5 months compared with 15.7 months in patients who never had surgery, supporting this strategy, Mejean said.

Discussing the results, Alexander Kutikov, MD, of Fox Chase Cancer Center, said that Carmena shows us that “we can harm patients by doing upfront cytoreductive nephrectomy.”

However, he noted that the combined approach can be applied to a very select group of patients. As an example, he pointed to a group of patients with metastatic RCC who may not require immediate systemic therapy. These may be excellent nephrectomy candidates, he said.

As a guide, Kutikov said, if you plan to observe without systemic therapy, proceed with cytoreductive nephrectomy.

“In everybody else, we should take great caution in offering cytoreductive nephrectomy because it absolutely can harm,” he said.