The combination of cabazitaxel and abiraterone was well tolerated and showed antitumor activity in previously treated patients with metastatic castration-resistant prostate cancer (mCRPC), according to a new phase I/II study.
“Therapeutic options for men with mCRPC have evolved considerably with the approval of five therapies associated with improved overall survival,” wrote study authors led by Christophe Massard, MD, PhD, of Gustave Roussy Cancer Campus in Villejuif, France. Still, “there is a need to provide robust evidence on how these agents should be used, in sequence or in combination, to achieve optimal medical management.
Two of these therapies are the androgen receptor-targeted abiraterone, and the taxane chemotherapy agent cabazitaxel. These drugs have partially overlapping mechanisms, so the researchers conducted a phase I/II trial of the two agents in combination. The phase I portion, to determine a maximum tolerated dose and any dose-limiting toxicities, included 10 patients (9 evaluable); the phase II portion, involving assessment of prostate-specific antigen (PSA) response, included 27 patients. The results were published online ahead of print in Annals of Oncology.
The phase I portion included patients who had progressive mCRPC after docetaxel treatment. Phase II patients had received docetaxel as well as at least 3 months of abiraterone prior to study entry.
There were no dose-limiting toxicities in the phase I study. Thus, the maximum tolerated dose was established as the full approved dosage of each of the two drugs: cabazitaxel 25 mg/m2 once every 3 weeks, and abiraterone 1,000 mg once daily.
Of 26 phase II patients who were evaluable, 12 (46.2%) achieved a PSA response (defined as at least a 50% decrease at 3 weeks or later). Six of those patients maintained the response for at least 6 months, while one patient maintained it for over 12 months; the median response duration was 6.7 months. The median PSA-progression-free survival was 6.9 months, and three of fourteen patients with measurable disease at baseline achieved a partial tumor response.
Adverse events (AEs) were similar across the two study phases; most treatment-emergent AEs were grade 1 or 2. In the phase II portion, the most common all-grade treatment-emergent AEs that were possibly related to the study drugs were asthenia (59%), nausea (41%), and diarrhea. Common grade 3/4 hematologic AEs included neutropenia (56%), leucopenia (52%), and lymphopenia (48%). Four patients died due to AEs including pneumonia, acute renal failure, septic shock, and acute coronary syndrome; none of those were deemed related to the study therapy.
The authors wrote that the rate of PSA declines support further evaluation of this combination in this patient population. “The response rate in our prospective phase II cabazitaxel and abiraterone combination study indicates that this combination is at least as active as cabazitaxel alone,” they wrote. “Randomized trials to ascertain the optimal sequencing and/or combination of these and other novel agents are urgently needed to maximize patient benefit.”