Mejean A, et al. - Experts evaluated whether upfront cytoreductive nephrectomy (CN) should continue to be performed before sunitinib in metastatic renal cell carcinoma. Findings did not suggest inferiority of sunitinib alone to CN followed by sunitinib in synchronous mRCC both in intermediate and poor MSKCC risk groups. For the requirement of medical treatment, CN should not be anymore the standard of care.

Methods

• A randomized phase III trial (CARMENA) was conducted on the patients (pts) with synchronous mRCC, amenable to CN. These were enrolled after confirmation of clear cell histology on biopsy if PS 0-1, absence of symptomatic brain metastasis, acceptable organ function and eligible for sunitinib therapy.
• Authors randomized the pts 1:1 to either CN followed by sunitinib (arm A) or sunitinib alone (arm B), and stratified by MSKCC risk groups.
• They adminstered sunitinib at 50 mg/d, 4/6wk with dose adaptation to routine practice.
• Sunitinib had to start 4 to 6 wk after surgery, in arm A.
• Overall survival (OS) was the primary endpoint.
• In order to demonstrate non inferiority hypothesis (H0: λE/λC > 1.20), with 80% power at a 1-sided significance level of 5%, a total of 576 pts had to be enrolled.

Results

• Findings suggested that 450 pts were included from 9/09 to 9/17, 226 and 224 in arm A and B, respectively.
• As per data, the median age was 62, ECOG-PS was 0 in 56% and 1 in 44%.
• MSKCC risk groups were intermediate/poor in 55.6/44.4% (arm A) and in 58.5/41.5% (arm B).
• Results demonstrated that 6.7% did not have CN and 22.5% never received sunitinib in arm A.
• In arm B, sunitinib was never administered in 4.9 % and 17% had secondary nephrectomy.
• Researchers noted that at the time of the analysis, 326 deaths have been observed with a median follow-up of 50.9 mo.
• In arm B, OS was not inferior, overall as well as by MSKCC risk groups (table).
• They did not observe any difference in response rate and PFS.
• They expected the safety of sunitinib in both arms.