Real-World Data Used to Inform Approval of Low-Dose Cabazitaxel for Prostate Cancer

Cabazitaxel can now be used at a dose of 20 mg/m² every 3 weeks in combination with prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) who have received a docetaxel-based treatment regimen. The approval followed an FDA review of a post-marketing study to evaluate a lower dose of the drug against the 25 mg/m² dose, which was approved for cabazitaxel in 2010.

The approval was based on data from a noninferiority, multicenter, randomized open-label trial (PROSELICA) of 1200 docetaxel-treated patients with mCRPC. Patients received either cabazitaxel 25 mg/m² (n = 602) or the 20 mg/m² (n = 598) dose.

The 2 doses were deemed at par in an intent-to-treat population: median overall survival (OS) was 13.4 months for patients administered 20 mg/m² cabazitaxel, compared with 14.5 months for patients administered the higher dose (hazard ratio [HR], 1.024; 97.78% CI, 0.886-1.184). The estimated median OS was 15.1 and 15.9 months for the low and the high dose, respectively (HR, 1.042; 97.78% CI, 0.886-1.224).

The higher dose, however, yielded safety concerns at a higher frequency than the lower dose of cabazitaxel. Major safety findings included myelosuppression, infections, and increased toxicity:

• Higher number of deaths in the last 30 days of the last study dose (5.4% vs 3.8%)
• Early infection-related deaths within a month of treatment initiation (1.3% vs 0.7%), primarily in those 60 and older
• Higher grade 3/4 infections (20% vs 10%)
• Febrile neutropenia (9% vs 2%)

Results from the FIRSTANA trial have also indicated that the lower dose is equally effective in ensuring survival and is relatively less toxic. The trial, results of which were published in the Journal of Clinical Oncology in July, evaluated the 2 doses of cabazitaxel in addition to 75 mg/m² docetaxel in an mCRPC population, administered every 3 weeks along with daily prednisone. While the median OS was 24.5 months in the low-dose arm, it was 25.2 months in the high-dose arm. However, grade 3/4 adverse events were much different: 41.2% vs 60.1%, respectively.

Current management strategies for cabazitaxel-associated toxicities include:

• Prophylactic antibiotics or granulocyte colony-stimulating factor for neutropenic complications
• Patient education and prompt intervention, such as an antidiarrheal, to overcome diarrhea
• Monitoring patients for fatigue.