Safety and efficacy of everolimus in patients with non-clear cell renal cell carcinoma refractory to VEGF-targeted therapy: Subgroup analysis of REACT.

402 Background: Metastatic non-clear cell renal cell carcinoma (mncRCC), which accounts for about 25% of all RCCs, is characterized by resistance to treatment and poor overall survival. Despite recent advances in targeted therapies for patients with mRCC, effective therapies for patients with mncRCC remain limited. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated to provide patients with mRCC of any histology refractory to VEGF-targeted therapy access to everolimus in advance of regulatory approval. Methods: REACT, an open-label, international, expanded-access program (Clinicaltrials.gov: NCT00655252 ) enrolled patients with measurable or nonmeasurable mRCC of any histology who were intolerant of, or progressed while on, VEGFR-TKI therapy in order to evaluate the long-term safety of everolimus 10 mg daily. Overall incidence of grade 3/4 and serious adverse events (AEs) were recorded, as was tumor response to everolimus according to RECIST criteria. A subgroup analysis of safety and efficacy in patients with mncRCC was performed. Results: Of 1367 patients enrolled, 75 patients (5.5%) had mncRCC. Median everolimus treatment duration in the mncRCC subgroup was 12.14 weeks (range, 0.9–49.0 weeks) and in the overall REACT population it was 14.0 weeks (range, 0.1–83.7 weeks). In the mncRCC subgroup, most commonly reported grade 3/4 AEs were anemia (17.3%), dyspnea (10.7%), pleural effusion (9.3%), fatigue (8.0%), and hyperglycemia (6.6%). Best overall response was similar in the mncRCC subgroup and overall population: respectively, 1.3% and 1.7% had partial response and 49.3% and 51.6% had stable disease. Conclusions: Although patients with mncRCC had a slightly lower treatment duration than the overall REACT population, approximately 50% of these patients achieved disease control on treatment. In this subgroup, everolimus was well tolerated, no new safety issues were observed, and the AE profile was consistent with that of the overall population. These encouraging results of the safety and efficacy of everolimus in patients with mncRCC support further evaluation of everolimus in these patients.