Overcoming resistance mechanisms in a study of cabozantinib (C) plus docetaxel (D) and prednisone (P) in metastatic castrate-resistant prostate cancer (mCRPC)

Authors

• FH Karzai
• RA Madan
• MR Theoret
• PM Arlen
• J Strauss
• G Chun
• A Couvillon
• N Harold
• C Chen
• NA Dawson
• SM Steinberg
• JB Trepel
• JJ Wright
• DK Price
• JL Gulley
• WD Figg
• WL Dahut

Abstract

D improves survival in mCRPC, but benefits are modest. Emerging clinical data suggests mCRPC patients (pts) treated with anti-androgen therapy like abiraterone (AA) or enzalutamide (ENZA) have decreased responses to susequent therapy with D due to cross-resistance in the androgen pathway targeted by D, AA, and ENZA(van Soest et al, Eur J Cancer 49:18, 2013). Patients (pts) with no prior history of D, receive D at 75 mg/m2 IV on day 1 of a 21 day cycle, and prednisone (P) at 5 mg po q12 hours, with C at three dose levels: 20 mg, 40 mg, or 60 mg po daily.19 pts have been accrued on phase I; 4 at 20 mg C, 8 at 40 mg C, and 7 at 60 mg C.On phase I, 13 patients previously treated with AA, the median potential follow up is 12.4 months. 9 month PFS is 60.5% (95% CI: 34.0%-82.0%).D plus P may have limited benefits after disease progression on AA as seen in 3 retrospective analyses demonstrating a median PFS of 4.6 months or less (Mezynski J, et al. Ann Oncol 23;11, 2012) (Aggarwal R, et al. Clin Genitourin Cancer 12;5, 2014) (Schweizer MT, et al. Eur Urol 66;4, 2014). PFS results seen in this trial compare favorably to historical data of treatment with D after progression on AA, suggesting the addition of C to D may help overcome acquired resistance.

Scientific Focus Area: Cancer Biology

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