FDA Approves Jevtana for Prostate Cancer Subset

Jevtana (cabazitaxel) was granted approval by the Food and Drug Administration (FDA) for the treatment of men with metastatic castration-resistant prostate cancer who previously received a docetaxel-containing regimen.

While the drug was previously approved at a dosage of 25 mg/m² every three weeks in this patient population in 2010, the current approval is for a regimen of 20 mg/m² every three weeks in combination with prednisone.

The approval is based on phase 3 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. 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.

The one-sided 98.89 percent 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 at least 50 percent of the OS benefit associated with C25 versus mitoxantrone in the TROPIC trial, with 95 percent CI. The UCI of the HR for C20 versus C25 could not exceed 1.214 under a one-sided 98.89 percent 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. Researchers observed similar rates in each arm for tumor, PSA, and pain progression. The most frequent PFS events were PSA progression and pain progression.

There was no significant difference in the tumor response rate in evaluable patients receiving C20 and C25 (18.5 percent vs 23.4 percent, respectively). Median time to tumor progression was nine months for patients receiving C20 and 9.3 months for patients receiving.

PSA response rates were significantly higher in the C25 arm, with 29.5 percent of C20 patients and 42.9 percent of C25 patients demonstrating a 50 percent or more decline in PSA from baseline. Median time to PSA progression was 6.8 months or longer for patients receiving C25 compared with 5.7 months in the C20 arm.

The safety population consisted of 580 patients assigned to C20 and 595 assigned to C25 who received at least one dose of Jevtana. Patients in the C20 group received a median of six treatment cycles for a median duration of 18 weeks. Patients in the C25 group received a median of seven 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 two 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.

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. The most frequent nonhematologic treatment-emergent AEs possibly related to study treatment in both Jevtana groups were diarrhea, nausea and fatigue.

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

In the C20 group, 41.8 percent experienced grade 3 or higher neutropenia compared with 73.3 percent of patients in the C25 group. Researchers observed grade 3 or higher febrile neutropenia in 2.1 percent of the C20 group and 9.2 percent of the C25 group. Eleven patients (1.9 percent) in the C20 arm reported grade 3 or higher hematuria versus 25 patients (4.2 percent) in the C25 arm. Incidence of grade 3 or higher 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 percent of patients assigned to the lower dose.

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