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

Gan, CL; Dudani, S; Wells, JC; Donskov, F; Pal, SK; Dizman, N; Rathi, N; Beuselinck, B; Yan, F; Lalani, AA; Hansen, A; Szabados, B; de Velasco, G; Tran, B; Lee, JL; Vaishampayan, UN; Bjarnason, GA; Subasri, M; Choueiri, TK; Heng, DYC

Author(s): Gan, CL; Dudani, S; Wells, JC; Donskov, F; Pal, SK; Dizman, N; Rathi, N; Beuselinck, B; Yan, F; Lalani, AA; Hansen, A; Szabados, B; de Velasco, G; Tran, B; Lee, JL; Vaishampayan, UN; Bjarnason, GA; Subasri, M; Choueiri, TK; Heng, DYC;
Details: Publication Year 2021-01-18,Volume 10,Issue #4,Page 1212-1221
Journal Title: Cancer Medicine
Abstract: BACKGROUND: Cabozantinib is approved for metastatic renal cell carcinoma (mRCC) based on the METEOR and CABOSUN trials. However, real-world effectiveness and dosing patterns of cabozantinib are not well characterized. METHODS: Patients with mRCC treated with cabozantinib between 2011 and 2019 were identified and stratified using the International mRCC Database Consortium (IMDC) risk groups. First- (1L), second- (2L), third- (3L), and fourth-line (4L) overall response rate (ORR), time to treatment failure (TTF), and overall survival (OS) were analyzed. Dose reduction rates and their association with TTF and OS were determined. RESULTS: A total of 413 patients were identified. The ORRs across 1L to 4L were 32%, 26%, 25%, and 29%, respectively, and the median TTF rates were 8.3, 7.3, 7.0, and 8.0 months, respectively. The median OS (mOS) rates in 1L to 4L were 30.7, 17.8, 12.6, and 14.9 months, respectively. For patients treated with 1L PD(L)1 combination agent (n = 31), 2L cabozantinib had ORR of 22%, median TTF of 5.4 months, and mOS of 17.4 months. About 50% (129/258) of patients required dose reductions. The TTF and mOS were significantly longer for patients who required dose reduction vs. patients who did not, with an adjusted hazard ratio of 0.37 (95% CI 0.202-0.672, p < 0.01) and 0.46 (95% CI 0.215-0.980, p = 0.04), respectively. Limitations include the retrospective study design and the lack of central radiology review. CONCLUSION: The ORR and TTF of cabozantinib were maintained from the 1L to 4L settings. Dose reductions due to toxicity were associated with improved TTF and OS. Cabozantinib has clinical activity after 1L Immuno-oncology combination agents.
Publisher: Wiley
Keywords: Imdc; cabozantinib; first line; fourth line; real-world; renal-cell carcinoma; response rates; second line; survival; third line
Research Division(s): Personalised Oncology
PubMed ID: 33463028
Publisher's Version: https://doi.org/10.1002/cam4.3717
Open Access at Publisher's Site: https://doi.org/10.1002/cam4.3717
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2021-03-09 08:05:49

Last Modified: 2021-03-09 08:44:05