Randomized phase 2 Cabazitaxel dose individualization and Neutropenia prevention Trial (CAINTA) in patients with metastatic castration-resistant prostate cancer.

PURPOSE: There is ongoing controversy about the recommended dose of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).

EXPERIMENTAL DESIGN: This multicenter phase II open-label, randomized, parallel-group study compared 3-weekly cabazitaxel at 25 mg/m2 (conventional Arm A) with cabazitaxel therapeutic drug monitoring (TDM) (experimental Arm B) in mCRPC. The primary objective was to improve the clinical feasibility rate (CFR) defined as the absence of grade 4 neutropenia or thrombocytopenia, any thrombocytopenia with bleeding, febrile neutropenia, severe non-hematological toxicity, withdrawal for cabazitaxel-related toxicity or death. 60 patients had to be randomized to detect a difference in CFR of 35% (power 80%, 2-sided alpha 10%).

RESULTS: 40 patients were randomized to Arm A and 33 patients to Arm B. CFR was 69.4% in Arm A and 64.3% in Arm B (p = 0.79). Week-12 PSA response was 38.5% in both arms. A radiological response by RECIST v.1.1 was seen in 3 (9.7%) patients in Arm A versus 6 (23.1%) patients in Arm B (P = 0.28), disease progression was higher in Arm A compared to Arm B (61.3% versus 30.8%, P = 0.05). Median PFS was longer in Arm B compared to Arm A (9.5 versus 4.4 months, HR = 0.46, P = 0.005). Median OS was higher in Arm B compared to Arm A (16.2 versus 7.3 months, HR = 0.33, P <0.0001).

CONCLUSIONS: Pharmacokinetic-guided dosing of cabazitaxel in patients with mCRPC is feasible and improves clinical outcome due to individual dose escalations in 55% of patients.