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Updated: Dec 30, 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 Study of Cabozantinib and Androgen Ablation in Patients with Hormone-Naïve Metastatic Prostate Cancer
Paul G Corn1, Miao Zhang2, Graciela M Nogueras-Gonzalez3
1Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. pcorn@mdanderson.org.
Purpose:
Cabozantinib, an oral inhibitor of c-MET/VEGFR2 signaling, improved progression-free survival (mPFS) but not overall survival (OS) in metastatic castrate-resistant prostate cancer. We evaluated cabozantinib plus androgen deprivation therapy (ADT) in hormone-naïve metastatic prostate cancer (HNMPCa).
Patients And Methods:
Patients received ADT plus cabozantinib starting at 60 mg daily. The primary endpoint was castrate-resistant PFS by radiographic criteria, clinical progression, or receipt of additional therapy. Secondary endpoints included OS, safety, radiographic responses, and biomarker modulation.
Results:
Sixty-two patients received treatment. With a median follow-up of 31.2 months, the mPFS was 16.1 months (95% CI, 14.6-22.7 months), and mOS was not reached. Reductions in PSA ≥ 90%, bone-specific alkaline phosphatase ≥ 50%, and urine N-telopeptides ≥ 50% occurred in 83%, 87%, and 86% of evaluable patients, respectively. Responses in bone scan and measurable disease were observed in 81% of and 90% of evaluable patients, respectively. Most common grade 3 adverse events were hypertension (19%), diarrhea (6%), and thromboembolic events (6%), and dose reductions occurred in 85% of patients. Analysis of baseline cytokine and angiogenic factors (CAFs) revealed that higher plasma concentrations of Lumican, CXCL5, CD25, and CD30 were associated with shorter PFS as was high tumor expression of pFGFR1.
Conclusions:
Cabozantinib plus ADT has promising clinical activity in HNMPCa. CAF profiles and tissue markers suggest candidate prognostic and predictive markers of cabozantinib benefit and provide insights for rational therapy combinations.
Insights
Cabozantinib combined with androgen deprivation therapy shows promising activity in hormone-naïve metastatic prostate cancer. Biomarkers may predict treatment response and guide future combination therapies.
Area of Science:
- Oncology
- Prostate Cancer Research
- Pharmacology
Background:
- Cabozantinib targets c-MET/VEGFR2 signaling.
- Previous studies showed improved progression-free survival but not overall survival in metastatic castrate-resistant prostate cancer.
Purpose of the Study:
- To evaluate the efficacy and safety of cabozantinib plus androgen deprivation therapy (ADT) in hormone-naïve metastatic prostate cancer (HNMPCa).
Main Methods:
- Sixty-two patients received ADT plus daily cabozantinib (60 mg).
- Primary endpoint: castrate-resistant progression-free survival (PFS).
- Secondary endpoints: overall survival (OS), safety, radiographic response, and biomarker modulation.
Main Results:
- Median PFS was 16.1 months; median OS was not reached.
- Significant reductions in PSA, bone-specific alkaline phosphatase, and urine N-telopeptides were observed.
- High response rates in bone scans (81%) and measurable disease (90%).
- Common grade 3 adverse events included hypertension (19%) and diarrhea (6%).
- Higher baseline plasma concentrations of Lumican, CXCL5, CD25, CD30, and tumor pFGFR1 expression correlated with shorter PFS.
Conclusions:
- Cabozantinib plus ADT demonstrates promising clinical activity in hormone-naïve metastatic prostate cancer.
- Cytokine and angiogenic factor profiles, along with tissue markers, may serve as prognostic and predictive biomarkers for cabozantinib treatment.
- Findings offer insights for developing rational combination therapy strategies.
