Cabozantinib After a Previous Immune Checkpoint Inhibitor in Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Analysis

Abstract

Background Angiogenesis has been recognized as the most important factor for tumor invasion, proliferation, and progression in metastatic renal cell carcinoma (mRCC). However, few clinical data are available regarding the efficacy of cabozantinib following immunotherapy. Objective To describe the outcome of cabozantinib in patients previously treated with immunotherapy. Patients and methods Patients with mRCC who received cabozantinib immediately after nivolumab were included. The primary endpoint was to assess the outcome in terms of efficacy and activity. Results Eighty-four mRCC patients met the criteria to be included in the final analysis. After a median follow-up of 9.4 months, median overall survival was 17.3 months. According to the IMDC criteria, the rates of patients alive at 12 months in the good, intermediate, and poor prognostic groups were 100%, 74%, and 33%, respectively (p < 0.001). The median progression-free survival (PFS) was 11.5 months (95% CI 8.3-14.7); no difference was found based on duration of previous first-line therapy or nivolumab PFS. The overall response rate was 52%, stable disease was found as the best response in 25.3% and progressive disease in 22.7% of patients. Among the 35 patients with progressive disease on nivolumab, 26 (74.3%) patients showed complete/partial response or stable disease with cabozantinib as best response after nivolumab. The major limitations of this study are the retrospective nature and the short follow-up. Conclusions Cabozantinib was shown to be effective and active in patients previously receiving immune checkpoint inhibitors. Therefore, cabozantinib can be considered a valid therapeutic option for previously treated mRCC patients, irrespective of the type and duration of prior therapies.Giampaolo Tortora and Giuseppe Procopio share the co-last authorship.

Cabozantinib real‐world effectiveness in the first‐through fourth‐line settings for the treatment of metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

“…The median number of prior therapies in this study was two. In a study of 84 patients who received prior checkpoint inhibitors, Iacovelli and colleague reported an impressive ORR of 52% and PFS of 11.5 months (95% CI 8.3–14.7) with the use of cabozantinib in the 3L and beyond setting 16 . These studies suggest that cabozantinib is active in the post IO setting.…”

Subgroup analysis of the AFTER I-O study: a retrospective study on the efficacy and safety of subsequent molecular targeted therapy after immune-oncology therapy in Japanese patients with metastatic renal cell carcinoma

“…Iacovelli et al. ( 16 ) only reported the correlation between the outcomes of I-O treatment and efficacy of subsequent therapy. Furthermore, certain reports are available regarding the efficacy of specific TT after I-O regimens ( 10 , 13 , 15 , 16 , 18–20 ).…”

Long progression-free survival with cabozantinib in a heavily pretreated patient with metastatic renal cell carcinoma: a case report

“…Cabozantinib showed efficacy and activity in 84 patients previously receiving immune checkpoint inhibitors irrespective of the type and duration of previous treatments, with a median OS of 17.3 months and a median PFS of 11.5 months (95% CI, 8.3-14.7). 13 Moreover, cabozantinib showed good safety and activity in an unselected population (96 patients) treated according to real-world data from an Italian Managed Access Program. 14 Cabozantinib was administered as second-line therapy in 28 patients (29%) and as third-line therapy in 18 patients (19%), while the remaining 50 patients (52%) received cabozantinib in further treatment lines.…”