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Updated: Oct 21, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
A Phase II, Randomized, Open-Label, Multi-arm Study of TAS-115 for Castration-Resistant Prostate Cancer Patients With
Nobuaki Matsubara1, Hirotsugu Uemura2, Satoshi Nagamori3
1Division of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Introduction:
TAS-115 is an oral multikinase inhibitor targeting the MET proto-oncogene, vascular endothelial growth factor receptor, and colony-stimulating factor 1 receptor. We evaluated the efficacy and safety of TAS-115 in castration-resistant prostate cancer (CRPC) patients with bone metastases.
Patients And Methods:
This phase II study, conducted in Japan, comprised 2 cohorts of CRPC patients. Cohort A included patients with bone metastasis and no history of docetaxel; TAS-115 200 to 400 mg/d was administered with abiraterone and prednisone. Cohort B included patients with symptomatic multiple bone metastases, post- or unfit for docetaxel, randomized 1:1 to receive TAS-115 400 or 600 mg/d orally, once daily, in a repeated weekly schedule of 5 days on/2 days off. The primary endpoint was bone scan index (BSI) response rate at Week 12 in each dose group.
Results:
Cohorts A and B included 24 and 26 patients, respectively. The 12-week BSI response rates for 200, 300, and 400 mg were 0%, 33.3%, and 16.7% in Cohort A, and for 400 and 600 mg were 7.1% and 25.0% in Cohort B. The best BSI response rates for 200, 300, and 400 mg were 0%, 66.7%, and 16.7% in Cohort A, and for 400 and 600 mg were 7.1% and 33.3% in Cohort B. A ≥ 30% reduction in BPI-SF score was shown in 57.7% of patients in Cohort B. The most frequent Grade ≥ 3 adverse drug reactions were hypophosphatemia (20.8%) in Cohort A and anemia (23.1%) in Cohort B.
Conclusion:
TAS-115 appears to demonstrate anti-tumor activity and acceptable tolerability in CRPC patients with bone metastases.
Insights
TAS-115 shows anti-tumor activity in castration-resistant prostate cancer (CRPC) patients with bone metastases. The oral multikinase inhibitor demonstrated acceptable tolerability and potential efficacy in this patient population.
Area of Science:
- Oncology
- Pharmacology
Background:
- Castration-resistant prostate cancer (CRPC) with bone metastases presents significant treatment challenges.
- Multikinase inhibitors offer a targeted approach for CRPC management.
Purpose of the Study:
- To evaluate the efficacy and safety of TAS-115, an oral multikinase inhibitor, in CRPC patients with bone metastases.
- To determine optimal dosing for TAS-115 in combination with abiraterone and prednisone, and as a monotherapy in docetaxel-experienced patients.
Main Methods:
- Phase II study in Japan with two cohorts of CRPC patients.
- Cohort A: bone metastasis, no prior docetaxel; TAS-115 (200-400 mg/d) with abiraterone and prednisone.
- Cohort B: symptomatic bone metastases, post- or unfit for docetaxel; TAS-115 (400 or 600 mg/d) randomized 1:1.
Main Results:
- 12-week bone scan index (BSI) response rates varied by dose and cohort, with best rates up to 66.7% in Cohort A and 33.3% in Cohort B.
- Over 57% of Cohort B patients showed a ≥ 30% reduction in bone pain.
- Frequent Grade ≥ 3 adverse events included hypophosphatemia (Cohort A) and anemia (Cohort B).
Conclusions:
- TAS-115 demonstrates anti-tumor activity in CRPC patients with bone metastases.
- The drug exhibits acceptable tolerability in this patient group.
- Further investigation into TAS-115's role in CRPC treatment is warranted.
