Scott T. Tagawa
ATLANTA — The combination of apalutamide, abiraterone acetate and docetaxel induced a high rate of PSA decline and measurable disease response with a manageable safety profile among men with metastatic castration-resistant prostate cancer, according to study results presented at American Association for Cancer Research Annual Meeting.
The CHAARTED and STAMPEDE trials showed the combination of androgen receptor inhibition plus taxane chemotherapy has clinical benefit. Thus, Scott T. Tagawa, MD, MS, medical director of the genitourinary oncology program at Weill Cornell Medicine and NewYork-Presbyterian, and colleagues sought to evaluate whether combining drugs that target different points in the androgen receptor signaling pathway is effective for men with castration-resistant disease.
“We generated preclinical data pointing toward synergy of directly targeting the androgen receptor pathway with abiraterone and indirectly targeting the pathway via microtubule stabilization with taxane chemotherapy,” Tagawa told HemOnc Today. “We also showed safety of the two-drug abiraterone/docetaxel combination in a prior study. That study, while small, looked like impressive activity.
“Based upon a current phase 3 study, a future standard-of-care therapy for patients with metastatic castration-resistant prostate cancer might be the combination of abiraterone and apalutamide,” he added. “Therefore, we wanted to test the safety of the triplet combination to set the stage for future efficacy studies.”
Tagawa and colleagues evaluated the combination of 1,000 mg daily abiraterone acetate, 75 mg/m2 docetaxel every 3 weeks and 5 mg twice-daily prednisone with two doses of apalutamide (Erleada, Janssen) — 120 mg daily or 240 mg daily — among nine men (median age, 69 years) with progressive metastatic castration-resistant prostate cancer. The men had a median PSA of 8.18 (range, 0.07-278.5), intact organ function, and no prior exposure to apalutamide ever or docetaxel within 3 years of enrollment.
The most common sites of metastasis included lymph nodes (78%) and bone (67%), followed by lung (11%) and other sites (11%).
Determination of dose-limiting toxicity and recommended phase 2 dose served as the study’s primary endpoints.
Three men received the 120-mg dose of apalutamide and six received the 240-mg dose. In the latter group, one man experienced grade 3 hypertension, a dose-limiting toxicity researchers deemed possibly related to treatment.
All men demonstrated at least a 95% PSA decline, and 78% experienced a 99% or greater PSA decline.
All five men with measurable disease had a 100% response per RECIST criteria.
“It is impressive that 100% of patients had major PSA reductions and all those that started with measurable disease had significant shrinkage,” Tagawa said. “Also, the full doses of all drugs were tolerable and not clearly different than giving the drugs alone.”
Further, six of seven men had undetectable post-treatment circulating tumor cell counts.
“The study is currently enrolling into an expansion cohort to provide additional data that will narrow the confidence intervals around response and toxicity rates,” Tagawa said. “In addition, one of the next steps will be to examine our biomarkers of response and resistance.” – by Alexandra Todak
Molina A, et al. Abstract CT097. Presented at: AACR Annual Meeting; March 29-April 3, 2019; Atlanta.
Disclosures: Janssen and the Department of Defense provided financial support for this study. Tagawa reports previous honoraria from Janssen as a consultant. Please see the abstract for all other authors’ relevant financial disclosures.