| General information |
| Database: | DB00206 |
| Objective: | Cabozantinib (XL184), an oral inhibitor of multiple receptor tyrosine kinases such as MET and VEGFR2, was evaluated in a phase II nonrandomized expansion study in castrationresistant prostate cancer (CRPC). |
| Authors: | Smith MR, et al |
| Title: | Cabozantinib in chemotherapypretreated metastatic castrationresistant prostate cancer: results of a phase II nonrandomized expansion study. |
| Journal: | J Clin Oncol. |
| Year: | 2014 |
| PMID: | 25225437 |
| Trial Design |
| Clinical Trial Id: | NCT00940225 |
| Agent: | cabozantinib
|
| Target: | Hepatocyte growth factor receptor, Vascular endothelial growth factor receptor 2
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | castrationresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II nonrandomized expansion open lable study |
| Key Patients Feature: | Eligible patients had ChemotherapyPretreated CRPC and bone metastases on bone scan, Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate hematologic and endorgan function. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | daily starting doses of 100 mg or 40 mg |
| Treatment Info: | Patients received openlabel cabozantinib at daily starting doses of 100 mg or 40 mg until disease progression or unacceptable toxicity. |
| Primary End Point: | bone scan response. |
| Secondary End Point: | Other efficacy end points included overall survival, pain, analgesic use, and biomarkers. |
| Patients Number: | 144 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Ninetyone patients (63%) had a bone scan response, often by week 6. Treatment resulted in clinically meaningful pain relief (57% of patients) and reduction or discontinuation of narcotic analgesics (55% of patients), as well as improvements in measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Improvements in each of these outcomes were observed in both cohorts: bone scan response in 73% and 45%, respectively; reductions in measurable soft tissue disease in 80% and 79%, respectively. |
| Disease Control Rate: | Improvements in each of these outcomes were observed in both cohorts: bone scan response in 73% and 45%, respectively; reductions in measurable soft tissue disease in 80% and 79%, respectively. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | Median overall survival was 10.8 months for the entire population. |
| Adverse Event(agent arm): | Most common grade 3 or 4 adverse events were fatigue (22%) and hypertension (14%). Fetheyr dose reductions because of toxicity were required in the 40mg group. |
| Conclusions: | The evidence suggests that cabozantinib has clinically meaningful activity in CRPC. Cabozantinib resulted in improvements in bone scans, pain, analgesic use, measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Taken together, thesephase II observations warrant further development of cabozantinib in prostate cancer. |