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Cabazitaxel is a second-generation taxane that was FDA approved to treat patients with metastatic castration-resistant prostate cancer (mCRPC) after it was shown to significantly prolong survival versus mitoxantrone in the TROPIC study (NEJM JW Oncol Hematol Dec 2010 and Lancet 2010 Oct 2; 376:1147). Now, as part of a post-marketing FDA requirement, international investigators have conducted two industry-sponsored, randomized phase III trials to provide additional findings regarding cabazitaxel dosing and sequencing in this setting.
In the FIRSTANA study, 1168 patients with chemotherapy-naive mCRPC were randomized to receive docetaxel at 75 mg/m2 (D75) or intravenous cabazitaxel at 20 mg/m2 (C20) or at the FDA-approved dose of 25 mg/m2 (C25) every 3 weeks plus prednisone. Median OS (the primary endpoint) was similar with D75, C20, or C25 (24.3, 24.5 and 25.2 months, respectively), as was progression-free survival. The objective response rate was nonsignificantly higher with C25 than with D75 (41.6% and 30.9%). The rates of grade 3 or 4 treatment-related toxicity were 60.1% with C25, 46.0% with D75, and 41.2% with C20.
In the PROSELICA study, 1200 mCRPC patients previously treated with docetaxel were randomized to receive C25 or C20 every 3 weeks. Median OS (the primary endpoint) was similar with C20 or C25 (13.4 and 14.5 months, respectively). Also, C20 was shown to be noninferior to C25 by maintaining ≥50% of the OS benefit achieved by C25 versus mitoxantrone in the TROPIC study. Health-related quality-of-life measures were also similar with either dose. However, grade 3 or higher treatment-related toxicity was less common with C20 (39.7% vs. 54.5%).
Oudard S et al. Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: A randomized phase III trial—FIRSTANA. J Clin Oncol 2017 Oct 1; 35:3189. (http://dx.doi.org/10.1200/JCO.2016.72.1068)
Eisenberger M et al. Phase III study comparing a reduced dose of cabazitaxel (20 mg/m2) and the currently approved dose (25 mg/m2) in postdocetaxel patients with metastatic castration-resistant prostate cancer—PROSELICA. J Clin Oncol 2017 Oct 1; 35:3198. (http://dx.doi.org/10.1200/JCO.2016.72.1076)
Comment
The FIRSTANA study provides evidence that OS is similar with docetaxel or cabazitaxel administered at 20 or 25 mg/m2 in chemotherapy-naive mCRPC patients, whereas the PROSELICA study shows that OS is similar with cabazitaxel at either dose in mCRPC patients previously treated with docetaxel. The previously approved, 25 mg/m2 dose of cabazitaxel at times required administration of white blood cell growth factor. This consideration is rare with the now-approved 20 mg/m2 dose, which should generally be considered the standard-of-care dose going forward.