897O - Cabozantinib (XL184) at 40 mg in patients with metastatic castration resistant prostate cancer (mCRPC): results of a phase 2 non-randomized expansio...

Date 30 September 2012
Event ESMO Congress 2012
Session Genitourinary tumors, prostate I
Topics Anticancer Agents
Prostate Cancer
Therapy
Biological Therapy
Presenter Johann De Bono
Authors J.S. De Bono1, M.R. Smith2, D.E. Rathkopf3, P.G. Corn4, D. Mukherji5, A. Harzstark6, O. Sartor7, D. Smith8, N. Tunariu9, C. Sweeney10
  • 1Royal Marsden Hospital, Sutton/UK
  • 2Hematology-oncology, Massachusetts General Hospital, 02114 - Boston/US
  • 3Medical Oncology, Memorial Sloan-Kettering Cancer Center, 10128 - New York/US
  • 4Dept. Of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 5Department Of Hematology Oncology Po Box: 11-0236, Royal Marsden Hospital & Institute of Cancer Research, SM2 5PT - Sutton/UK
  • 6Medical Oncology, University of California San Francisco, 94115 - San Francisco/US
  • 7Department Of Medicine And Urology, Tulane University School of Medicine, 70112 - New Orleans/US
  • 8Department Of Internal Medicine, University of Michigan, Ann Arbor/US
  • 9Urology, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research ICR, SM25PT - Sutton/UK
  • 10Lank Center For Genitourinary Oncology, Dana Farber Cancer Institute, 02115 - Boston/US

 

Abstract

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.

Disclosure

M.R. Smith: Consultant to Exelixis.

O.A. Sartor: Consultant for Exelixis.

All other authors have declared no conflicts of interest.