CABOSEQ: The efficacy of cabozantinib post up-front immuno-oncology combinations in patients with advanced renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

Abstract

318 Background: There are limited data to understand the activity of cabozantinib (CABO) as second line (2L) therapy post standard of care ipilimumab-nivolumab (IPI-NIVO) or immuno-oncology(IO)/vascular endothelial growth factor (VEGF) inhibitor combinations (IOVE). The activity of subsequent 3L approved therapies post CABO has not been established. Methods: Using the IMDC dataset, we examined all patients who received 2L CABO. We sought to identify the overall response rate (ORR), time to treatment failure (TTF) and overall survival (OS) of 2L CABO after IPI-NIVO, approved IOVE combinations and other 1L approaches. Additionally, we examined these outcomes for patients that received an approved 3L treatment post 2L CABO. Hazard ratios were adjusted for IMDC risk groups. Results: 346 patients were identified who had all received 2L CABO (78 post 1L IPI NIVO, 46 post 1L IOVE, 222 post 1L other). Of the entire cohort, 12.6%, 62.6% and 24.8% were IMDC favourable, intermediate and poor risk, respectively. 84% had clear cell histology, 18.5% had a sarcomatoid component and 38.3% had bone metastases at diagnosis. Outcomes for patients that received 2L CABO, stratified by 1L therapy are outlined in the table, followed by outcomes for patients that received subsequent 3L therapy post 2L CABO. After adjustment for IMDC criteria, the HR for 2L CABO OS and TTF for IOVE vs IPI-NIVO were 1.73 (95% CI 0.83-3.62 p = 0.14) and 1.62 (0.89-2.95 p = 0.11), respectively. Conclusions: There is clinically meaningful activity of CABO post IPI-NIVO, IOVE and other standard 1L approved therapies. Broadly, time to event endpoints and response rates are similar irrespective of 1L therapy. Approved systemic therapies post CABO, mainly single agent VEGF inhibitors also have activity, though as expected this is diminished compared to earlier lines of therapy. These are real world benchmarks with which to counsel our patients when using single agent CABO.[Table: see text]

Impressive reduction of brain metastasis radionecrosis after cabozantinib therapy in metastatic renal carcinoma: A case report and review of the literature

“…After first-line nivolumab–ipilimumab therapy, the median time to failure for cabozantinib is 6.90 months ( 32 ) with a median OS of 21.44 months and 37.9% of ORR ( 33 ). More data of cabozantinib as a second-line therapy will be revealed by the ongoing trial CaboPoint ( 34 ).…”

An Evaluation of Cabozantinib for the Treatment of Renal Cell Carcinoma: Focus on Patient Selection and Perspectives

“… 47 , 48 Recently, the CABOSEQ trial has focused on assessing the efficacy of cabozantinib in second-line settings, using data from the IMDC cohort database. 49 Among the 346 patients identified, 78 had been previously treated with nivolumab-ipilimumab, 46 with ICI-TKI, and 222 with another type of treatment. The IMDC risk scores were good for 12.6% of these patients, intermediate for 62.6%, and poor for 24.8%.…”

Metastatic Clear-Cell Renal Cell Carcinoma in the Era of Immune Checkpoint Inhibitors: Therapies and Ongoing Trials

“…Cabozantinib is another option that serves as a PD-1 inhibitor alternative, and is available for patients with IMDC intermediate- or poor risk disease [ 26 ]. Recent studies have moved towards evaluating the efficacy of cabozantinib in the real-world setting, reporting it as a commonly utilized VEGF therapy and increasingly used as 2 L therapy after dual ICI therapy [ 27 , 28 , 29 , 30 ].…”