Abstract
BackgroundThe recommended starting dose of cabazitaxel for castration-resistant prostate cancer (CRPC) is 25 mg/m2 in Japan and Europe. Although lower doses are established alternatives based on randomized controlled trials, the safety and efficacy of 25 and 20 mg/m2 in real-world settings are not well established. Therefore, we investigated the safety and efficacy of cabazitaxel at the recommended starting dose or a lower dose (20 mg/m2) in real-world clinical practice.MethodsWe compared the safety and efficacy of cabazitaxel between patients who received cabazitaxel at starting doses of 25 and 20 mg/m2 (C25 and C20, respectively) in a Japanese post-marketing surveillance study of 662 patients with docetaxel-refractory CRPC. Safety was assessed in terms of adverse drug reactions (ADRs). Prostate-specific antigen (PSA) response rate, overall survival (OS), and time-to-treatment failure (TTF) were compared between the C25 and C20 groups in unmatched patients and after applying propensity score matching.ResultsThe C20 and C25 groups comprised 190 and 159 patients without matching and 112 patients per group after matching. In unmatched patients, any-grade (C25 vs C20: 89.3% vs 78.4%, Fisher’s p < 0.01) and grade ≥ 3 (81.1% vs 61.1%) ADRs were more frequent in the C25 group. Neutropenia (any grade: 61.6% vs 54.2%; grade ≥ 3: 55.3% vs 42.6%) and febrile neutropenia (grade ≥ 3: 30.2% vs 14.7%) were more frequent in the C25 group. In matched patients, the PSA response rate (reduction in PSA ≥30% from a baseline ≥5 ng/mL) was 26.4 and 32.0% in the C20 and C25 groups, respectively, median OS was 291 days (95% CI 230–not reached) versus not reached (hazard ratio 0.73, 95% CI 0.50–1.08), and TTF favored C25 (hazard ratio 0.75, 95% CI 0.57–0.99).ConclusionsClinicians should consider the patient’s risk of clinically significant ADRs and prophylactic granulocyte colony stimulating factor when selecting the starting dose of cabazitaxel for CRPC. Some patients at high risk of ADRs or unfit patients may benefit from a lower starting dose of 20 mg/m2, whereas fit patients may be candidates for a starting dose of 25 mg/m2.Trial registrationNot applicable.
Highlights
The recommended starting dose of cabazitaxel for castration-resistant prostate cancer (CRPC) is 25 mg/m2 in Japan and Europe
Some patients at high risk of Adverse drug reaction (ADR) or unfit patients may benefit from a lower starting dose of 20 mg/m2, whereas fit patients may be candidates for a starting dose of 25 mg/m2
There were some apparent differences between the 20 mg/m2 cabazitaxel (C20) and compared with 25 mg/m2 (C25) groups for several baseline characteristics, including Eastern Cooperative Oncology Group (ECOG) Performance status (PS), Prostate-specific antigen (PSA) at baseline, medical history, complications, switching from docetaxel, and palliative radiation therapy (Table 1)
Summary
The recommended starting dose of cabazitaxel for castration-resistant prostate cancer (CRPC) is 25 mg/m2 in Japan and Europe. We investigated the safety and efficacy of cabazitaxel at the recommended starting dose or a lower dose (20 mg/m2) in real-world clinical practice. Cabazitaxel is a second-generation taxane that was approved in the US in 2010 and Europe in 2011 following the international TROPIC study [8]. It was subsequently approved in Japan in 2014 based on pharmacokinetic studies confirming its pharmacokinetics and safety in Japanese patients were consistent with global findings [9, 10]. Some studies suggested that a lower dose of 20 mg/m2 might be appropriate in consideration of safety [13, 14], and in some cases, adverse events (AEs) can be managed by patient monitoring and reducing the dose of cabazitaxel [15]
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