Randomized phase II study of nintedanib in metastatic castration-resistant prostate cancer postdocetaxel.
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.
aDepartment 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.
Jean-Pierre
JP
Droz
Jaques
J
Medioni
Christine
C
Chevreau
Helene
H
De Mont-Serrat
Michael
M
Merger
Peter
P
Stopfer
Rolf
R
Kaiser
Stephane
S
Oudard
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000627:therapeutic use; D050257:Tubulin Modulators / Q000627:therapeutic use
D000970:Antineoplastic Agents; D007211:Indoles; D043823:Taxoids; D050257:Tubulin Modulators; D000077143:Docetaxel; C530716:nintedanib