Weekly versus 3-weekly cabazitaxel for the treatment of castration-resistant prostate cancer: A randomised phase II trial (ConCab)

Publication date: July 2018
Source:European Journal of Cancer, Volume 97
Author(s): Jeffrey Yachnin, Bjørnar Gilje, Kristian Thon, Hemming Johansson, Yvonne Brandberg, Theocharis Panaretakis, Anders Ullén
AimPatients treated with cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC) may experience dose delays and reductions or terminate treatment because of toxicity. A lower and more frequent dose of cabazitaxel could improve dose intensity.Patients and methodsThis prospective, multi-center, phase II study randomly assigned 101 patients to Arm A, cabazitaxel Q3W, 25 mg/m² or Arm B, Q1W, 10 mg/m² 5 of 6 weeks. The primary end-point was dose intensity, and we hypothesised that the experimental arm (Arm B) would result in a 20% absolute increase in the relative cumulative dose by week 18. Secondary end-points were overall survival (OS), progression-free survival (PFS), pain progression, radiological and prostate-specific antigen (PSA) response rates, quality of life (Functional Assessment of Cancer Therapy Prostate) and tolerability.ResultsMedian doses of cabazitaxel were 276 mg (45–320) and 257 mg (20–330) in Arms A and B, respectively, at week 18 (p = 0.13). More patients in Arm B stopped treatment because of toxicity. Median PFS in Arms A and B were 6.0 and 6.4 months (hazard ratio [HR] 0.73, 95% confidence interval [CI]: 0.47–1.13, p = 0.156) and for OS, 14.6 and 15.6 months (HR 0.95, CI: 0.58–1.58, p = 0.85), respectively. PSA responses ≥50% were seen in 52% and 46% of patients in Arms A and B, respectively. A higher incidence of febrile neutropenia was observed in the standard arm (10 events versus 1, p < 0.008). A grade V febrile neutropenia occurred in Arm A. Low-grade haematuria was more prevalent with weekly cabazitaxel (15 events versus 5, p = 0.003). Three patients in Arm B experienced clinically significant inflammation of the ureters. A toxicity is not previously described for cabazitaxel.ConclusionWeekly cabazitaxel reduces the incidence of febrile neutropenia but does not increase the dose intensity compared with the standard therapy. Cabazitaxel has clinical meaningful efficacy in heavily pre-treated patients with mCRPC.



https://ift.tt/2LNpTjC