Efficacy of cabozantinib (C) after PD-1/PD-L1 checkpoint inhibitors in metastatic renal cell carcinoma (mRCC): The Gustave Roussy experience

Abstract

Background: Optimal treatment sequence in mRCC remains unclear, although PD-1/ PD-L1 inhibitors are becoming standard of care in second or third-line. There is little evidence about the efficacy of antiangiogenic therapies after immune checkpoint inhibitors (ICI), especially of C, which was recently approved for mRCC. We report our initial experience of C efficacy after prior ICI. Method(s): We conducted a retrospective analysis of mRCC patients (pts) enrolled on clinical trials at Gustave Roussy with ICI with a special focus on C as subsequent therapy. Clinical outcome during C treatment, including Time to Treatment Failure (TTF), Objective Response Rate (ORR), Overall Survival (OS) and safety are reported. Result(s): After a median follow-up of 60 months (mo), among 127 pts treated with ICI (n: 107; nivolumab), 44 (35%) were still on-treatment and 5 pts had stable disease after treatment interruption. Among the 78 pts who progressed after ICI, 22 pts (28%) never received further treatment. 56 pts (72%) received further therapies: 18 (32%) C, 25 (44%) Axitinib (A) and 13 (24%) other (O). C was given as third-line or beyond in 27% and 73% of pts, respectively. Before starting C, pts were only intermediate or poor prognosis by IMDC criteria. Considering all evaluable pts, ORR was 33%, median TTF was 7.99 mo and median OS was 12.33 mo. Focusing on C, ORR was 42% and no pts presented progressive disease as best response versus 37% for A with 2% progressive disease. Currently, median TTF and OS on C are not yet estimable (0.92-not reached); update on clinical outcome will be presented. Moreover, C demonstrated acceptable safety profile and the rate of treatment discontinuation because of adverse events was 11%. Conclusion(s): In mRCC pts previously treated by ICI, treatment with C seems to be very active, irrespective of number of prior treatments or IMDC risk group. Prior PD- 1/PD-L1 exposure did not influence safety of subsequent C therapy. Interestingly, activity of A also appears excellent, raising the hypothesis of enhanced efficacy of TKI after ICI.