Sunitinib After Nephrectomy Benefits Some Patients with Advanced Kidney Cancer
Nephrectomy has been the standard of care in metastatic renal-cell carcinoma for 20 years. However, its role in treating patients with advanced disease in the era of targeted therapy has been brought into question. In the CARMENA study, researchers assessed the benefit of initial nephrectomy followed by targeted therapy with sunitinib (Sutent) in patients with metastatic kidney cancer versus the benefits provided by sunitinib monotherapy. Sunitinib is a small-molecule inhibitor of multiple receptor tyrosine kinases (Méjean A, et al. N Engl J Med. 2018;379:417-427).
CARMENA was a prospective, multicenter, open-label, randomized, phase 3 trial that included 450 patients with metastatic clear-cell renal carcinoma at the time of diagnosis to determine whether initial nephrectomy is necessary before sunitinib treatment. All patients were suitable candidates for nephrectomy. Patients were stratified as intermediate or poor risk according to the Memorial Sloan Kettering Cancer Center criteria.
The patients were randomized in a 1:1 ratio to undergo nephrectomy followed by sunitinib or to sunitinib alone. In the sunitinib-only arm, sunitinib was given at 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. In the surgery arm, sunitinib was initiated 3 to 6 weeks after nephrectomy. The median follow-up for the entire study population was 50.9 months, and the primary end point was overall survival (OS).
The median OS was noninferior in the sunitinib arm versus the nephrectomy followed by sunitinib arm (18.4 months vs 13.9 months, respectively); this was also observed for the intermediate- and poor-risk groups. For the intermediate-risk cohort, the median OS was 19 months versus 23.4 months, respectively. For poor-risk patients, the median OS was 10.2 months versus 13.3 months, respectively. No significant differences were observed in objective response rates and progression-free survival between the 2 arms.
Overall, 38.1% of patients had a grade 3 or 4 adverse event (32.8% in the surgery arm and 42.7% in the sunitinib monotherapy arm). The most common grade 3 or 4 adverse events in the sunitinib arm were asthenia (9.9%), hand-foot syndrome (5.6%), anemia (5.2%), and neutropenia (4.7%).
“Although nephrectomy may have a role in controlling symptoms in some patients with metastatic renal-cell carcinoma…there is no ‘one size fits all’ approach,” the researchers concluded. “The multimodal approach of individualized treatment provides appropriate management of metastatic renal-cell carcinoma.”