Related Experiment Video
Updated: Apr 29, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Randomized phase II study of nintedanib in metastatic castration-resistant prostate cancer postdocetaxel
Jean-Pierre Droz1, Jaques Medioni, Christine Chevreau
1aDepartment of Medical Oncology, Centre Léon-Bérard, Claude Bernard Lyon-1 University, Lyon bMedical Oncology Department, Georges Pompidou European Hospital (HEGP), Paris cDepartment of Medical Oncology, Institut Claudius Regaud, Toulouse dBoehringer Ingelheim France S.A.S, Reims, France eBoehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Abstract:
This open-label, phase II trial assessed the efficacy and safety of two doses of nintedanib, a triple angiokinase inhibitor targeting vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor signaling, in patients with metastatic castration-resistant prostate cancer (mCRPC) following progression on docetaxel-based regimens. Patients were randomized to nintedanib 150 mg (arm A, n=40) or 250 mg (arm B, n=41) twice daily for 6 months unless disease progression or adverse events (AEs) led to discontinuation. The primary endpoint was the prostate-specific antigen (PSA) response rate (confirmed PSA decline of ≥20% from baseline). Eighty-one patients were enrolled. The PSA response rate was 0% (0/32) in arm A versus 11.1% (4/36) in arm B (P=0.12); 5.6% of patients (2/36) in arm B showed a PSA reduction of at least 50%. In arm B, the rate of PSA increase was significantly decelerated on treatment versus before treatment (P=0.002). The median progression-free survival was 73.5 and 76.0 days for arm A and arm B, respectively (P=0.3). AEs included gastrointestinal disorders, asthenia, hypertension, and reversible elevated transaminases. The incidence of drug-related serious AEs (no drug-related deaths) was 20.0% (arm A) and 24.4% (arm B). The primary endpoint was not met. Nintedanib (250 mg) showed only modest activity with manageable AEs in patients with mCRPC post-docetaxel.
Insights
This phase II trial found nintedanib did not meet its primary endpoint in metastatic castration-resistant prostate cancer (mCRPC) patients. The 250mg dose showed modest activity and manageable side effects, but did not significantly improve PSA response rates.
Area of Science:
- Oncology
- Clinical Pharmacology
- Medical Oncology
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) remains a significant challenge, especially after docetaxel progression.
- Targeting angiogenesis pathways is a key strategy in mCRPC treatment.
- Nintedanib is a triple angiokinase inhibitor with potential anti-cancer activity.
Purpose of the Study:
- To evaluate the efficacy and safety of two nintedanib doses in mCRPC patients post-docetaxel.
- To determine the prostate-specific antigen (PSA) response rate as the primary endpoint.
- To assess progression-free survival and adverse events associated with nintedanib treatment.
Main Methods:
- An open-label, randomized phase II trial involving 81 patients with mCRPC.
- Patients received either nintedanib 150mg or 250mg twice daily for 6 months or until disease progression/adverse events.
- Primary endpoint: confirmed PSA decline of ≥20% from baseline.
Main Results:
- The primary endpoint was not met; PSA response rates were 0% (150mg) and 11.1% (250mg).
- A PSA reduction of ≥50% was observed in 5.6% of patients in the 250mg arm.
- Median progression-free survival was similar between arms (73.5 vs 76.0 days).
- Common adverse events included gastrointestinal disorders and asthenia; serious adverse events occurred in 20-24% of patients.
Conclusions:
- Nintedanib, particularly at 250mg, demonstrated modest activity in mCRPC patients post-docetaxel.
- The drug was associated with manageable adverse events.
- Further investigation may be warranted, but the primary efficacy endpoint was not achieved.
