Lower Dose Cabazitaxel Noninferior For Docetaxel-Treated mCRPC

Men with metastatic castration-resistant prostate cancer post-docetaxel may be given a reduced dose of cabazitaxel without losing overall survival benefit

medwireNews: The PROSELICA trial results support the use of a toxicity-sparing dose of cabazitaxel, where necessary, in men with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel.

Overall survival (OS) was a median of 13.4 months for the 598 patients randomly assigned to receive a 1-hour cabazitaxel infusion at 20 mg/m2 on day 1 of a 21-day cycle and 14.5 months for the 602 patients who were given a 25 mg/m2 infusion. Both patient groups also received prednisone 10 mg/day.

Thus, cabazitaxel 20 mg/m2 met the phase III trial's noninferiority criteria, defined as maintenance of at least 50% of the OS benefit achieved by cabazitaxel 25 mg/m2 versus mitoxantrone in the TROPIC study of mCRPC, the authors report in the Journal of Clinical Oncology.

Progression-free survival was comparable in the two treatment arms (median 2.9 vs 3.5 months), as were secondary endpoints including tumour response rate (18.5 vs 23.4%), time to tumour progression (median 9.0 vs 9.3 months) and pain response (34.7 vs 37.3%).

But the 20 mg/m2 dose was statistically inferior to the 25 mg/m2 regimen with regard to the secondary endpoints of a prostate-specific antigen (PSA) decrease of 50% or more (29.5 vs 42.9%) and time to PSA progression (median 5.7 vs 6.8 months, hazard ratio=1.2).

“Therefore, [25 mg/m2] may still be an appropriate starting dose, and if subsequent dose reduction becomes necessary, particularly for myelosuppression, the dose of cabazitaxel may be reduced to 20 mg/m2 without detriment to patient outcome”, say lead investigator Mario Eisenberger, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland, USA, and co-workers.

They highlight the lower rate of grade 3 or 4 treatment-emergent adverse events with the cabazitaxel 20 mg/m2 regimen than the original dose, at 39.7% versus 54.5%. In particular, grade 3 or more severe neutropenia occurred in 41.8% of patients given the low-dose cabazitaxel regimen versus 73.3% of those given the 25 mg/m2 dose, with febrile neutropenia rates of 2.1% and 9.2%, respectively.

“PROSELICA provides further evidence of the efficacy of cabazitaxel in the treatment of patients with mCRPC who have previously received docetaxel”, the authors conclude.

“Data also suggest that patients can achieve a similar clinical benefit from cabazitaxel at both the 20 and 25 mg/m2 starting doses and that dose reductions may be implemented in patients who require them without significant detriment to outcome.”


Eisenberger M, Hardy-Bessard A-C, Kim CS, 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; Advance online publication 15 August 2017. DOI https://doi.org/10.1200/JCO.2016.72.1076

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