Cabozantinib 40mg Dose ESMO Abstract:
897O | CABOZANTINIB (XL184) AT 40 MG IN PATIENTS WITH METASTATIC CASTRATION RESISTANT PROSTATE CANCER (MCRPC): RESULTS OF A PHASE 2 NON-RANDOMIZED EXPANSION COHORT (NRE)
J.S. De Bono1, M.R. Smith2, D.E. Rathkopf3, P.G. Corn4, D. Mukherji1, A.L. Harzstark5, O.A. Sartor6, D.C. Smith7, N. Tunariu1, C. Sweeney2
1Sutton/UK, 2Boston, MA/US, 3New York/US, 4Houston, TX/US, 5San Francisco, CA/US, 6New Orleans, LA/US, 7Ann Arbor, MI/US
Background
Cabozantinib (cabo) inhibits MET & VEGFR2. In a phase 2 NRE cohort of patients (pts) with mCRPC, cabo at 100 mg daily was associated with high rates of bone scan resolution, pain relief & overall disease control, independent of PSA changes. We now report the activity & safety of cabo 40 mg daily.
Methods
Docetaxel (D)-pretreated (=225 mg/m) CRPC pts with bone metastasis were required to have progressed within 6 months of last dose of D. Tumor response was assessed q6 wks. Bone scan response used computer-aided assessment of bone scan lesion area (BSLA). Diffusion Weighted MRI was performed in some pts. Pain intensity (worst pain over the past 24 hrs; BPI scale 0-10) & interference with sleep & daily activity were prospectively assessed using an IVR system (7 day intervals). Analgesic use was collected by diary. Bone turnover markers & circulating tumor cells (CTCs) were assessed.
Results
51 pts were enrolled. Among 30 pts who had =6 wks f/u, the median age was 66 yrs. 20% received cabazitaxel, 70% abiraterone, & 20% had visceral disease. 47% (14/30) had pain (BPI =4) at baseline (bsl) of which 86% (12/14) were using narcotics. Median bsl CTC count was 17 & 73% had =5. Median f/u was 84 days (range, 44-141). 55% (11/20 pts) with a f/u bone scan showed BSLA reduction (range, 1-70%). Increases in Apparent Diffusion Coefficient (suggestive of tumor necrosis) & enhancement reduction were observed in bone & soft tissue metastases. 10/14 pts (71%) evaluable for pain response had a =30% reduction from bsl; 7/12 (58%) pts decreased narcotics. Sleep & daily activity improved in pts with pain relief. Among pts with elevated bsl serum levels of CTx, NTx & bALP, 57%, 60% & 33% respectively, had declines =30%. In 22 pts with CTCs =5, 59% had a decrease of =30% at wks 6 or 12, & 23% converted to <5 CTCs. 5 (17%) pts required a dose reduction. The most common Gr 3/4 AEs were hypertension (13%), decreased appetite (7%), & back pain (7%).
Conclusions
Cabo 40 mg was well tolerated & demonstrated bone scan resolution, substantial pain relief with a narcotic sparing effect, & reductions in bone turnover markers & CTCs in heavily pretreated mCRPC pts. MRI results are consistent with an anti-tumor effect.
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