235 Background: Docetaxel (D) improves overall survival in metastatic castrate-resistant prostate cancer (mCRPC), but benefits remain short-lived. Clinical data suggests patients (pts) with mCRPC treated with anti-androgen therapy like abiraterone (AA) or enzalutamide (ENZA) have decreased responses to subsequent therapy due to cross-resistance in the androgen pathway targeted by D, AA, or ENZA(van Soest et al, Eur J Cancer 49:18, 2013). Combining D with other agents, like cabozantinib (C), could target different cellular signaling pathways potentially minimizing tumor resistance. Methods: D naive pts receive 75 mg/m2 IV on day 1 of a 21 day cycle, and prednisone (P) 5 mg po q12 hours with C at 3 dose levels: 20, 40, or 60 mg po daily until maximum tolerated dose (MTD) is defined. In phase 2, pts who have progressed on AA or ENZA, enroll on a randomized 2 arm cohort comparing D plus C to D alone. Results: 20 pts have been accrued; 4 at 20 mg C, 8 at 40 mg C, and 7 at 60 mg C. On phase 2, 1 pt is randomized to D alone. Median age is 68 (44-84 yrs). Median baseline PSA is 94.7 (0.01-754.1 ng/mL). Gleason score is 9 (7-10). Median cycles is 9.5 (1-33). 8 pts have bone only disease, 12 pts have bone and soft tissue disease. Common grade 2 and grade 3 adverse events possibly related to C: hand/foot syndrome (4/16), oral mucositis (4/16), hypophosphatemia (4/16), and fatigue (3/16). The MTD of C is 40 mg daily with D. 15 pts were previously treated with AA or ENZA. In 13 patients previously treated with AA, median PFS has not been reached, with a median potential follow up of 12.4 months. Six month PFS is 77.8% and 9 month PFS is 60.5%. Conclusions: D plus P may have limited benefits after disease progression on AA as seen in 3 retrospective analyses demonstrating a median PFS survival 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 previously published data of treatment with D after AA in mCRPC, suggesting the addition of C to D may help overcome acquired resistance. Further randomized trials will determine if C in combination with D will enhance clinical outcomes. Clinical trial information: NCT01683994.
Indirect treatment comparison of cabazitaxel for patients with metastatic castrate-resistant prostate cancer who have been previously treated with a docetaxel-containing regimen
