Medical Oncology Institut de Cancérologie de Lorraine Nancy, Lorraine, France
Background: Despite metastatic renal cell carcinoma (mRCC) expanded treatment armatorium with VEGFR tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI), disease progression ultimately occurs for most patients. Rechallenge may be a compelling strategy when no new treatment option is available. Cabozantinib is standard of care in first and later lines of therapy, but its activity in a rechallenge setting is unknown.
Methods: This study assess the efficacy and safety of cabozantinib rechallenge, as defined by a second exposure after an interval of at least 3 months without treatment or at least one other treatment line, in patients with mRCC. For this retrospective study, data were collected from medical files. Primary endpoint was median progression-free survival (PFS) at rechallenge. Secondary endpoints were duration of treatment (DOT), overall survival (OS), objective response rate (ORR), time-to-treatment failure (TTF), and safety at rechallenge. This study was approved by local ethic committee.
Results: We included 51 patients from 9 centers in France who received cabozantinib rechallenge between 2017 and 2022. Median age at diagnosis was 54 years, 78.4% were male, 90.2% had clear cell mRCC and 92.2% had prior nephrectomy. 15 patients (29.4%) were rechallenged after a pause in treatment, whereas 36 (70.6%) had one or more other treatment lines between first cabozantinib exposure (CABO-1) and rechallenge (CABO-2). Median PFS was 15.1 mo (95% CI 11.2-22.1) at CABO-1 and 14.4 mo (95% CI 9.8-NR) at CABO-2, and median OS was 67.6 mo for CABO-1 (95% CI 52.2-NR) and 27.4 mo for CABO-2 (95% CI 17.2-NR). Rechallenge in the subgroup of patients who had CABO-1 PFS < 6 months display significant activity (CABO-2 PFS 14.9mo and CABO-2 OS 57.1mo). The safety did not show unexpected adverse events.
Conclusions: Cabozantinib rechallenge is a feasible treatment option with potential clinical benefit for mRCC patients.