ASCO GU 2018: Visceral Metastases on Abiraterone vs. Placebo: A Post-hoc Analysis of Mode of Radiographic Progression In COU-AA-302

San Francisco, CA (UroToday.com) Dr. Teply and colleagues presented a post-hoc analysis of COU-AA-302 [1] assessing mode of radiographic progression. Abiraterone prolongs survival in patients with prostate cancer due to its potent inhibition of androgen synthesis. Increased rates of visceral metastatic disease at the time of progression on abiraterone compared to baseline demonstrate a poor prognostic feature associated with non-AR dependent prostate cancer. The authors hypothesized that the rate of development of visceral disease is increased with abiraterone compared to other treatments without potent androgen signaling inhibition. Thus, the objective of this study was to examine the time to visceral disease among patients treated with abiraterone vs placebo using the COU-AA-302 (chemotherapy naïve) trial data.

For this study, the authors performed a post-hoc analysis of radiographic progression data for the phase III study of abiraterone vs placebo [1] among 1088 patients enrolled in the trial. Data were censored at end of study treatment. The distribution of cumulative incidence for visceral metastases was calculated by the Kaplan-Meier method and compared with the log-rank test. Multivariable cox regression analysis was performed to assess for the independent association of study treatment (abiraterone vs placebo) with the development of visceral metastases. Over a median follow-up of 12.5 months, 84 of 1088 patients (7.7%) developed visceral metastases. Univariate log-rank testing showed no difference in time to visceral metastasis between the placebo and treatment groups (p = 0.97). The 1- and 3-year cumulative incidence of visceral metastases rates were estimated at 6.4% and 15.6% for abiraterone and 4.6% and 17.0% for placebo, respectively. On multivariable assessment, study treatment was not a significant predictor for the development of visceral metastasis (HR 0.76; 95% CI 0.47-1.21) after adjusting for baseline metastatic disease burden (soft tissue and bone) and LDH.

Dr. Teply concluded that abiraterone acetate was not associated with increased visceral metastases at the time of progression compared to placebo. This data may suggest to oncologists that abiraterone is not driving prostate cancer to a more aggressive phenotype characterized by visceral metastases. This certainly is becoming increasingly important as abiraterone continues to be used in early disease states.

Speaker: Benjamin Teply, University of Nebraska Medical Center, Omaha, NE

Co-Authors: Fang Qiu, Emmanuel S. Antonarakis, Michael Anthony Carducci, Samuel R. Denmeade

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@zklaassen_md at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

References:
1. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138-148.
2. Schweizer MT, Zhou XC, Wang H, et al. The influence of prior abiraterone treatment on the clinical activity of docetaxel in men with metastatic castration-resistant prostate cancer. Eur Urol. 2014;66(4):646-652.
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