(047) Comparison of Standard Versus Lower Initial Dose of Cabozantinib in Renal Cell Carcinoma and Hepatocellular Carcinoma: A Retrospective Analysis of Tolerability and Clinical Outcomes (Top Ten Poster)

Poster Abstract:

Background:
Cabozantinib is a multi-kinase inhibitor used for the treatment of several cancers, including renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Management of adverse effects often requires supportive care interventions, reactive dose reductions, and dose interruptions. Lower initial dosing strategies have been employed in clinical practice to improve tolerability, but evidence demonstrating improved tolerability without compromising clinical efficacy is lacking.
Objective(s):
To assess the tolerability and clinical outcomes of patients with RCC or HCC who initiated lower-dose (LD) ( < 60 mg QD) or standard-dose (SD) (60 mg QD) single-agent cabozantinib.

Methods:
A single-center, retrospective chart review of patients initiated on single-agent cabozantinib for first-line (1L) or subsequent-line (2L+) treatment of RCC or 2L+ treatment of HCC between January 1, 2018, and August 31, 2023, was conducted. The primary endpoint was the rate of dose reductions between LD and SD groups. Key secondary endpoints were time-to-first-dose-reduction (TTFDR), time-to-treatment-discontinuation (TTTD), time-to-next-treatment (TTNT), and overall survival.

Results:
Among the 134 eligible patients, 73 (54%) initiated LD cabozantinib and 61 (46%) initiated SD cabozantinib. Twenty patients received cabozantinib for 1L RCC (LD=11, SD=9), 92 for 2L+ RCC (LD=47, SD=45), and 22 for 2L+ HCC (LD=15, SD=7). The incidence of patients requiring dose reductions was 38% (n= 28) in the LD group and 61% (n=37) in the SD group (p < 0.05). Average TTFDR was 4 mo in the LD group and 2.4 mo in the SD group (p < 0.05). Average TTTD (7.7 mo vs. 10.8 mo; p=ns) and average TTNT (8.2 mo vs. 12.6 mo; p=ns) did not show significant differences between LD and SD groups. The most common treatment-related adverse effects that led to dose reductions were palmar-plantar erythrodysesthesia, fatigue, and diarrhea.
Discussion/conclusion:
LD cabozantinib was associated with a lower incidence of dose reductions and extended the time to first dose reduction compared to SD cabozantinib. Clinical outcomes were unaffected by the reduced initial dose.

References (must also be included in final poster): 1- Maroto P, Porta C, Capdevila J, et al. Cabozantinib for the treatment of solid tumors: a systematic review. Ther Adv Med Oncol. 2022;14:17588359221107112. Published 2022 Jul 13. doi:10.1177/17588359221107112

2- NCCN Guidelines: Kidney Cancer. Version 1.2024.

3- NCCN Guidelines: Hepatocellular Carcinoma. Version 2.2023.

4- Schmidinger M, Danesi R. Management of Adverse Events Associated with Cabozantinib Therapy in Renal Cell Carcinoma. Oncologist. 2018;23(3):306-315. doi:10.1634/theoncologist.2017-0335

5- Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17(7):917-927. doi:10.1016/S1470-2045(16)30107-3

6- Choueiri TK, Hessel C, Halabi S, et al. Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression-free survival by independent review and overall survival update [published correction appears in Eur J Cancer. 2018 Nov;103:287]. Eur J Cancer. 2018;94:115-125. doi:10.1016/j.ejca.2018.02.012

7- Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018;379(1):54-63. doi:10.1056/NEJMoa1717002