Background: Cabozantinib is an oral MET/VEGFR2 inhibitor.
A recent phase II study of cabozantinib (100mg daily) demonstrated improved bone scans in subjects with metastatic castration-resistant prostate cancer (mCRPC), but adverse events (AEs) caused frequent dose reductions. This study was designed to determine the efficacy and tolerability of cabozantinib at lower starting doses.
Patients and Methods: An adaptive design was used to determine the lowest active daily dose among 60mg, 40mg, and 20mg. The primary endpoint was week 6 bone scan response, defined as ≥30% decrease in bone scan lesion area. The secondary endpoint was change in circulating tumor cells (CTCs).
Results: Among 11 evaluable subjects enrolled at 40mg, there were 9 partial responses (PRs), 1 complete response, and 1 stable disease (SD). Of 10 subjects subsequently enrolled at 20mg, there were 1 PR, 5 SDs, and 4 with progressive disease. Among 13 subjects enrolled on the 40mg expansion cohort, there were 6 PRs and 7 SDs. No subjects required dose reduction or treatment interruption at 6 or 12 weeks; 3 subjects at dose level 0 discontinued due to AEs by 12 weeks. At 40mg, median treatment duration was 27 weeks. 58% of subjects with ≥5 CTCs/7.5mL at baseline converted to < 5.
Conclusions: Cabozantinib 40mg daily was associated with a high rate of bone scan response. Cabozantinib 40mg daily was associated with better tolerability than previously reported for cabozantinib 100mg daily. These observations informed the design of phase III studies of cabozantinib in mCRPC.
Written by:
Lee RJ, Saylor PJ, Michaelson MD, Rothenberg SM, Smas ME, Miyamoto DT, Gurski CA, Xie W, Maheswaran S, Haber DA, Goldin JG, Smith MR. Are you the author?
Massachusetts General Hospital Cancer Center, Harvard Medical School.
Reference: Clin Cancer Res. 2013 Apr 3. Epub ahead of print.
doi: 10.1158/1078-0432.CCR-13-0319
PubMed Abstract
PMID: 23553848
