Arnaud Méjean, MD, PhD
In an interim analysis of the French phase III noninferiority Carmena trial reported in The New England Journal of Medicine, Arnaud Méjean, MD, PhD, of the Hôpital Européen Georges Pompidou, and colleagues found that sunitinib alone was not inferior in overall survival vs nephrectomy followed by sunitinib in patients with intermediate- or poor-risk metastatic clear cell renal cell carcinoma.
In the trial, 450 patients who were candidates for nephrectomy from mostly French centers (25 patients from other European sites) were randomly assigned between September 2009 and September 2017 to receive sunitinib alone (n = 224) or nephrectomy followed by sunitinib (n = 226). Sunitinib was given at 50 mg per day in cycles of 28 days on and 14 days off every 6 weeks. In the nephrectomy group, sunitinib was initiated between 3 and 6 weeks after nephrectomy. Randomization was stratified according to Memorial Sloan Kettering Cancer Center prognostic risk of intermediate or poor. The primary endpoint was overall survival in the intent-to-treat population.
At the planned interim analysis (data cutoff in December 2017), median follow-up was 50.9 months. In the nephrectomy-sunitinib group, 16 patients (7.1%) did not undergo nephrectomy and 40 (17.7%) did not receive sunitinib; in the sunitinib group, 11 patients (4.9%) did not receive sunitinib and 38 (17.0%) underwent subsequent nephrectomy a median of 11.1 months after randomization for symptom control.
Median overall survival was 18.4 months in the sunitinib group vs 13.9 months in the nephrectomy-sunitinib group (stratified hazard ratio [HR] = 0.89, 95% confidence interval [CI] = 0.71–1.10, within the upper boundary of the 95% CI for noninferiority of ≤ 1.20). Median overall survival was 23.4 vs 19.0 months in the intermediate-risk subgroup (HR = 0.92, 95% CI = 0.68–1.24) and 13.3 vs 10.2 months in the poor-risk subgroup (HR = 0.86, 95% CI = 0.62–1.17). Median progression-free survival was 8.3 months vs 7.2 months (HR = 0.82, 95% CI = 0.67–1.00). Subsequent anticancer therapies were received by 51.3% vs 50.4% of patients. Objective response rates were 29.1% vs 27.4%.
Among all patients who actually received sunitinib, grade 3 or 4 adverse events occurred in 42.7% of the sunitinib alone group vs 32.8% of the nephrectomy-sunitinib group (P = .04). The most common grade 3 or 4 adverse events were asthenia (9.9% vs 8.6%), hand-foot syndrome (5.6% vs 4.3%), and anemia (5.2% vs 2.7%).
The investigators concluded, “Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal cell carcinoma who were classified as having intermediate-risk or poor-risk disease.”
Méjean A, et al: N Engl J Med 379:417-427, 2018.