Cabozantinib in patients (pts) with non-locally pretreated brain metastases (BM) from renal cell carcinoma (RCC): Results of the multicenter CABRAMET phase II trial (NCT03967522).

533 Background: Despite dramatic progress in metastatic RCC treatments, pts with BM remain with poor outcome and were mostly excluded from clinical trials. Local treatments on BM are standard today. Methods: Adult pts with histologically proven RCC and BM ≥ 5 mm (or > 8 mm if solitary) including at least one non-locally pretreated, < 3 prior systemic treatments excluding cabozantinib, ECOG PS 0 or 1 and steroids < 40 mg/day were included. Primary endpoint was BM progression free survival rate at 6 months (6m-BM-PFS) according to modified RANO-BM criteria by central review. Secondary endpoints were BM response and response duration, extracranial response, PFS, overall survival and safety. 25 evaluable pts were required to evaluate the main endpoint. Results: 26 pts were included, 25 were evaluable for the primary endpoint and median follow up time was 39.8 months [5.9-49.7]. The 6m-BM-PFS was 56.0% [unilateral 95%CI 37.9-] (14/25 pts). BM response was partial response (PR) for 61.5% (16/26) pts and median duration of response was not reached, 66.7% pts being event-free 24 months after BM response. Extracranial response was PR for 38.5% (10/26). Median PFS was 8.1 months [95%CI 4-11.9], and median BM PFS 8.4 months [95%CI 5.4-NR]. Median overall survival was 15.8 months [95%CI 9.7-35.0]. No new safety signals were observed. Conclusions: This is the first prospective trial assessing cabozantinib in RCC pts with non-locally pretreated BM. These results confirm the efficacy of cabozantinib on BM previously reported in retrospective series. Clinical trial information: NCT03967522 . Pts characteristics. Pts number N = 26 Median age (years) [range] 67 [44-86] Gender: F / M, n 5 / 21 ECOG PS: 0 / 1,n 10 / 16 RCC: non-clear cell / clear cell, n 2 / 24 Prior nephrectomy : n 16 Number of BM: 1 / 2 / >3, n 9 / 7 / 10 Prior BM treatments: Overall/ Surgery/ Radiation, n 10 / 3 / 10 Prior systemic treatment: 0 / 1 / >2, n 7 / 15 / 4 IMDC: Favorable / Intermediate / Poor, n 7 / 10 / 9