ESMO 2017: Stereotactic Ablative Radiotherapy (SABR) for Oligoprogressive Metastatic Castration-Resistant Prostate Cancer (mCRPC) During Abiraterone Therapy: A Phase I Study

Madrid, Spain (UroToday.com) Dr. Urban Emmenegger and colleagues from Toronto, Ontario, Canada presented their phase I trial design for using stereotactic ablative radiotherapy (SABR) for patients with oligoprogressive metastatic castration-resistant prostate cancer (mCRPC) while on abiraterone treatment at today’s poster session at ESMO 2017 in Madrid, Spain. Indeed, there are a subset of men with mCRPC who may present at some point with oligometastases, a state between loco-regional and widespread metastatic disease with metastases being limited both in number and location.

Oligoprogression is a situation where ≤ 3-5 metastatic tumor sites progress, while all other metastases are controlled by ongoing systemic therapy. At this point, typical practice would be to change systemic therapy, however SABR has emerged as a treatment option for oligometastatic or oligoprogressive disease sites. SABR may improve survival and delay the need to change systemic therapy, however some patients may derive limited benefit because of early and widespread metastatic progression following SABR. While there are no validated biomarkers to predict who may benefit from SABR, circulating tumor DNA (ctDNA) is a minimally invasive and highly informative biomarker which may assist with making this delineation. In the absence of published evidence on the use of SABR for oligoprogressive mCRPC in men undergoing abiraterone therapy, the author’s objective of this phase I study is to determine the incidence of acute and late toxicities associated with delivering SABR to all oligoprogressive metastatic sites in men with mCRPC on abiraterone.

Trial design: This phase I study will assess the primary endpoint of acute and late toxicities associated with delivering SABR to all oligoprogressive metastatic sites in 30 men with mCRPC on abiraterone therapy. Using conventional imaging, eligible mCRPC candidates will be identified based on ≤ 5 SABR amenable progressive metastatic lesions (≤ 3 in any one organ system) while all other metastases remain stable or are responding to abiraterone therapy. Before SABR, ctDNA will be collected from eligible patients to perform gene copy number and mutational analyses of prostate cancer relevant genes as a means to predict sustained responses to SABR. Secondary endpoints will include assessing preliminary efficacy data for parameters such as time to biochemical, radiological and/or symptomatic progression following SABR.

Speaker: Urban Emmenegger, Sunnybrook Hospital, Toronto, Canada

Co-Authors: S. Cheng (Toronto, Canada) K. Zukotynski (Hamilton, Canada) P. Cheung (Toronto, Canada)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain