Results of the phase 2 CABOPRE trials shared during the 2021 ESMO Congress showed that perioperative cabozantinib (Cabometyx) is feasible with early signs of clinical activity in patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC).1
Patients with favorable responses to systemic therapy have been suggested as the ideal candidates for cytoreductive nephrectomy (CN). In both the first and second lines of therapy cabozantinib may be a beneficial treatment for those with intermediate or poor risk mRCC.
The CABOPRE trial accrued patients with mRCC and an ECOG performance status of 0 or 1. The primary end point was overall response rate (ORR) prior to CN at week 12. Secondary end points include progression-free survival (PFS), overall survival (OS), safety and tolerability. The exploratory end point was molecular and pathological changes in biomarkers.
In total, 18 patients were enrolled across 4 University Hospitals in Spain between December 2018 and December 2020. Patients included were 18 years of age or older, suitable for CN surgery, have measurable disease, adequate organ function, and no prior therapy for mRCC.
During the study, all patients received cabozantinib at 60mg daily for 12 weeks. Cabozantinib was halted at least 28 days prior to CN and was restarted upon adequate wound healing.
The median age of patients included was 56.5 years (range, 49.0-63.0), with 66.6% being male and 66.6% have a performance status of 1. Most, 77.7%, were of intermediate risk. The mean primary tumor size was 96 mm and 100% had clear cell histology. Of the 16 patients evaluable, CN was performed on 11 of them.
The median PFS was 12.7 months, with the 12-month PFS rate being 56%. The 12-month OS rate was 70%, according to the Kaplan-Meier curve. In total 15 patients were included in the end point analysis and the ORR at 12 weeks was 26.7% at a 95% confidence interval. Three patients were not evaluable for response. Partial responses were seen in 26.7% of patients, stable disease was seen in 66.7% of patients, and progressive disease was seen in 6.7% of patients.
Sixty-one differently expressed miRNAs were correctly classified post treatment with cabozantinib. miRNA testing was done using the Nanostring miRNA expression panel V3. According to investigators, dynamic biomarkers may be key for treatment assessment.
All 18 patients were evaluated for safety. Common all-grade adverse events (AEs) included asthenia (67%), hypertension (55%), diarrhea (55%), mucositis (39%), hyperoxia (33%), hand-foot syndrome (22%), dysphonia (16%), hypothyroidism (16%). Only 1 incidence of grade 3/4 asthenia was reported.
1. Velasco G, Alonso T, Francisco J, et al. CABOPRE: A phase II study of cabozantinib (cabo) prior cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC). Presented at the 2021 ESMO Virtual Congress. September 16-20. Abstract 676P.