Optimizing the Upfront Treatment of mRCC

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Ongoing clinical trials may help shed light on an optimal frontline treatment for patients with metastatic renal cell carcinoma (mRCC). Two of these trials, CARMENA and SURTIME, are exploring surgery followed by sunitinib compared with sunitinib followed by surgery for patients with mRCC. Results from these phase III studies may provide guidance for the upfront utilization of nephrectomy. However, Brian I. Rini, MD, believes the investigations may include more intermediate risk patients, unlike similar studies that were conducted in the 80's, perhaps biasing the results.

Findings from the phase II RECORD-3 study reinforced frontline VEGF inhibition as a standard of care, Sumanta Kumar Pal, MD, notes. In this trial, first-line everolimus and second-line sunitinib was compared with the reverse sequence for patients with mRCC. Overall, the study failed to demonstrate noninferiority for first-line everolimus compared with sunitinib.

On the standard 4 weeks on/2 weeks off (4/2) schedule of sunitinib, patients are likely to experience toxicity, particularly during weeks 3 and 4, notes Nizar M. Tannir, MD. To address this, an alternative schedule of 2 weeks of sunitinib followed by 1 week of rest (2/1) was explored.

A retrospective analysis examined outcomes for patients who switched from 4/2 to 2/1 after the first occurrence of side effects. Overall, the alternative schedule was shown to mitigate adverse events while nearly doubling overall survival, Tannir states. In the analysis, the median overall survival with the 4/2 schedule was 17.7 months compared with 33.0 months with the 2/1 schedule.

A second analysis looked at patients who started at 2/1 compared with 4/2. This analysis also demonstrated an improvement in survival for the alternative dose, Tannirs states. Until prospective data is available, it is difficult to justify starting at the 2/1 schedule, Rini believes. However, if adverse events occur, the alternative schedule should be considered preferentially to a dose reduction.