Cabazitaxel regimen does not improve outcomes in high-risk prostate cancer
SAN FRANCISCO — The addition of cabazitaxel to neoadjuvant abiraterone acetate did not improve tumor response among men with high-risk prostate cancer, according to randomized phase 2 study results presented at ASCO Genitourinary Cancers Symposium.
Researchers reported no difference in complete response or minimal residual disease rates between those who received cabazitaxel (Jevtana, Sanofi Genzyme) and those who did not. However, across treatment groups, patients who achieved complete response or minimal residual disease negativity fared better.
“Genetic profiling of baseline and radical prostatectomy tissue is planned to identify predictors of response [and] treatment resistance,” Neil E. Fleshner, MD, MPH, FRCSC, head of the division of urology at University Health Network and chair of the division of urology at University of Toronto, said during a presentation.
Men with high-risk prostate cancer who receive unimodal therapy are at considerable risk for recurrence. The benefit of neoadjuvant therapy prior to radical prostatectomy has not been clearly established.
The ACDC-RP study included 78 men with high-risk prostate cancer.
Researchers assigned 38 men (mean age, 63.2 years; mean PSA, 37 ng/dL) to receive 6 months of abiraterone acetate (Zytiga, Janssen) dosed at 1,000 mg daily, along with prednisone and leuprolide dosed at 22.5 mg every 3 months.
The other 39 men (mean age, 62.3 years; mean PSA, 37.9 ng/dL) received the same regimen plus cabazitaxel dosed at 20 mg/m2 every 21 days for six cycles.
All study participants were candidates for radical prostatectomy and were considered surgically resectable. They had no evidence of metastatic or nodal disease and had received no more than 3 months of prior androgen deprivation therapy.
Rate of pathologic complete response or minimal residual disease after neoadjuvant treatment served as the primary outcome. Researchers defined minimal residual disease as 5% or less of prostate volume involved by tumor.
Secondary objectives included evaluations of the effect on PSA dynamics, surgical outcomes and pharmacodynamic markers. Investigators also assessed safety and evaluated the mechanism of treatment by genomics.
Seventy men completed the full course of their assigned treatment and underwent radical prostatectomy (cabazitaxel, n = 37; no cabazitaxel, n = 33).
Thirty-one men achieved either complete response or minimal residual disease, including 16 (43%) in the cabazitaxel group and 15 (45%) in the no-cabazitaxel group. Five men (cabazitaxel, n = 2) achieved complete response and 26 men (cabazitaxel, n = 14) exhibited minimal residual disease.
Kaplan-Meier analysis showed no significant difference in biochemical-free survival rate between treatment groups. However, men who achieved complete response or minimal residual disease-negative status achieved significantly longer biochemical-free survival.
“Not surprisingly, a significant percentage of patients had node-positive disease even though conventional imaging was negative,” Fleshner said.
Analysis of nodal status showed 18 men (26%) with N0 disease (cabazitaxel, n = 12; no cabazitaxel, n = 6) and 52 men (74%) with N1 disease (cabazitaxel, n = 25; no cabazitaxel, n = 27).
Researchers reported no difference in freedom from biochemical failure or pathologic outcomes between treatment groups.
“Interestingly, those patients who achieved either complete response or minimal residual disease did have a trend toward better PSA failure, and I expect over time that will get better,” Fleshner said.
Two of the first three men treated on the trial experienced grade 3 thrombotic events (deep vein thrombosis, n = 1; pulmonary embolism, n = 1), prompting investigators to stop the trial for a few months so they could amend it. From that point on, protocol mandated 28 days of low-molecular-weight heparin postoperatively for all study participants.
Overall, men assigned cabazitaxel appeared more than twice as likely to experience grade 3 adverse events (23% vs. 10%). The most common grade 3 adverse events that occurred among cabazitaxel-treated men included hepatotoxicity (10% for cabazitaxel vs. 5% for on cabazitaxel), febrile neutropenia (8% vs. 0%) and hypertension (5% vs. 5%).
“In terms of future directions, we need to learn more about what determines complete response and minimal residual disease,” Fleshner said. “We are taking this farther with an ongoing umbrella trial using a form of personalized genome-based assignment to see if we can further home in on personalization of this treatment schema. In this particular case, I think having [prostate-specific membrane antigen] PET scan would have perhaps eliminated a lot of patients who failed only for the fact they had unknown nodal disease.”
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Fleshner NE, et al. Abstract 224. Presented at: ASCO Genitourinary Cancers Symposium; Feb. 17-19, 2022; San Francisco.