New Cabazitaxel Dosage Approved for mCRPC

JASON HARRIS
Monday, September 18, 2017
Talk about this article with nurses and others in the oncology community in the General Discussions Oncology Nursing News discussion group.
FDA approval was given to a new regimen of cabazitaxel (Jevtana) to treat men with metastatic castration-resistant prostate cancer who previously received a docetaxel-containing regimen. The approval is for 20 mg/m2 every 3 weeks in combination with prednisone. The agency approved a dose of 25 mg/m2 every 3 weeks in this patient population in 2010.

The approval is based on phase III results from the PROSELICA trial published earlier this year. That data showed that the lower-dose regimen was noninferior for overall survival (OS) and was associated with a similar safety profile.

Median OS for patients assigned to the 20 mg/m2 dose (C20) was 13.4 months versus 14.5 months for those assigned to the 25 mg/m2 dose (C25; hazard ratio [HR], 1.024). Based on the per-protocol population, the estimated median OS was 15.1 for the C20 group and 15.9 months for the C25 group (HR, 1.042; 97.78% CI, 0.886-1.224).

The one-sided 98.89% upper boundary of the confidence interval (UCI) of the HR was 1.184, which was less than the 1.214 noninferiority margin, thus satisfying the predefined criteria for noninferiority in the intent-to-treat population of patients.

Noninferiority was defined as maintenance of ≥50% of the OS benefit associated with C25 versus mitoxantrone in the TROPIC trial, with 95% CI. The UCI of the HR for C20 versus C25 could not exceed 1.214 under a one-sided 98.89% CI after interim analyses. Secondary endpoints included progression-free survival (PFS), prostate-specific antigen (PSA), tumor and pain responses and progression, health-related quality of life, and safety.

Median progression-free survival (PFS) was 2.9 months in the C20 arm verse 3.5 months in patients receiving C25 (HR, 1.099; 95% CI, 0.974-1.240). Researchers observed similar rates in each arm for tumor, PSA, and pain progression. The most frequent PFS events were PSA progression (C20, 39.8%; C25, 34.7%) and pain progression (C20, 25.8%; C25, 28.1%).

There was no significant difference in the tumor response rate in evaluable patients receiving C20 and C25 (18.5% vs 23.4%, respectively; nominal P = .1924). Median time to tumor progression was 9.0 months for patients receiving C20 and 9.3 months for patients receiving C25 (HR, 1.096; 95% CI, 0.902-1.331).

PSA response rates were significantly higher in the C25 arm, with 29.5% of C20 patients and 42.9% of C25 patients demonstrating a ≥50% decline in PSA from baseline (nominal P<.001). Median time to PSA progression was 6.8 months or longer for patients receiving C25 compared with 5.7 months in the C20 arm (HR, 1.195; 95% CI, 1.025-1.393).

The safety population consisted of 580 patients assigned to C20 and 595 assigned to C25 who received at least 1 dose of cabazitaxel. Patients in the C20 group received a median of 6 treatment cycles for a median duration of 18 weeks. Patients in the C25 group received a median of 7 treatment cycles for a median duration of 21 weeks.

Researchers observed no significant difference in the number of patients who experienced a pain response and the rate of pain progression was similar in the 2 groups. Median time to pain progression was 6.2 months for patients receiving C20 versus 6.4 months for patients assigned to C25, with a similar risk for pain progression in both groups (HR, 1.046; 95% CI, 0.874-1.251).

More patients receiving C25 had dose delays and reductions compared with patients receiving C20. The most common treatment-emergent adverse event (AE) leading to death was neutropenic sepsis (C20, 0.2%; C25, 0.5%). The most frequent nonhematologic treatment-emergent AEs possibly related to study treatment in both cabazitaxel groups were diarrhea, nausea, and fatigue.

More patients in the C25 arm experienced serious treatment-emergent AEs (30.5% vs 43.2%). Overall, 95 patients (16.4%) assigned to C20 discontinued treatment due to toxicity, along with 19.5% of the C25 cohort.

In the C20 group, 41.8% experienced grade ≥3 neutropenia compared with 73.3% of patients in the C25 group. Researchers observed grade ≥3 febrile neutropenia in 2.1% of the C20 group and 9.2% of the C25 group. Eleven patients (1.9%) in the C20 arm reported grade ≥3 hematuria versus 25 patients (4.2%) in the C25 arm. Incidence of grade ≥3 alopecia, fatigue, and neuropathy was low in both arms.

One-fifth of patients in the C25 arm reported grade 3/4 infections compared with 10% of patients assigned to the lower dose.

Deaths within 30 days of the last study drug dose (5.4% vs 3.8%), and early infection-related deaths within 30 days of the treatment initiation (1.3% vs 0.7%) were more common in the C25 arm. All of the early infection-related deaths occurred in patients older than 60 years of age.

Talk about this article with nurses and others in the oncology community in the General Discussions Oncology Nursing News discussion group.
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