For patients receiving targeted therapies for metastatic renal cell carcinoma, outcomes are similar with sunitinib alone versus nephrectomy followed by sunitinib, concludes a trial in The New England Journal of Medicine.
The phase 3 randomized Clinical Trial to Assess the Importance of Nephrectomy (CARMENA) included 450 patients with biopsy-confirmed metastatic renal cell carcinoma, enrolled at 79 centers in France and other European countries. All were suitable candidates for nephrectomy followed by sunitinib. Memorial Sloan Kettering Cancer Center risk category was intermediate risk in about 58% of patients and poor risk in 42%.
After risk stratification, patients were assigned in a 1:1 ratio to nephrectomy followed by sunitinib (standard treatment) or sunitinib alone. Sunitinib dose schedule was 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. The main study endpoint was overall survival.
At planned interim analysis, with a median follow-up of 50.9 months, 326 patients had died. There was no significant difference in overall survival—the stratified hazard ratio for death fell below the specified boundary for noninferiority. Median overall survival was longer with sunitinib alone versus nephrectomy followed by sunitinib: 23.4 versus 19.0 months in the intermediate-risk group and 13.3 versus 10.2 months in the poor-risk group.
Response rate and progression-free survival were similar with or without nephrectomy. There was evidence of clinical benefit in 47.9% of patients in the sunitinib-alone group versus 36.6% in the nephrectomy-sunitinib group. Adverse events were as expected; dose reduction occurred in about 30% of both groups.
Cytoreductive nephrectomy has long been the standard of care for metastatic renal cell carcinoma. In recent years, new targeted therapies have emerged, including the vascular endothelial growth factor receptor inhibitor sunitinib. Few previous studies have directly compared the benefits of nephrectomy versus targeted therapy.
This randomized trial finds sunitinib alone noninferior to nephrectomy followed by sunitinib in patients with intermediate- or poor-risk metastatic renal cell carcinoma. The findings contrast with those of retrospective studies reporting a survival benefit of nephrectomy in patients receiving targeted therapies.
“Although nephrectomy may have a role in controlling symptoms in some patients…there is no ‘one size fits all’ approach,” the investigators conclude [Méjean A, et al. Sunitinib alone or after nephrectomy in metastatic renal cell carcinoma. N Engl J Med 2018; DOI: 10.1056/NEJMoa1803675].