ASCO GU 2020: Next-Generation Sequencing of Tumor Tissue from >4000 Men with Metastatic Castration-Resistant Prostate Cancer: The PROfound Phase III Study Experience

San Francisco, CA (UroToday.com) Approximately a quarter of patients with metastatic castration resistant prostate cancer harbor genomic alterations in DNA damage repair genes including genes involved in homologous recombination repair. Alterations in these genes have been thought to confer sensitivity to PARP inhibitors, as shown by the TOPARP-A and TOPARP-B studies. The PROfound study presented initially at ESMO 2019, stratified men with CRPC and DNA changes in homologous recombination repair genes who had progressed on either enzalutamide or abiraterone to either olaparib or the alternative anti-androgen. This study showed superior radiographic progression free survival with olaparib, and a suggestion of survival benefit, though survival data were immature at the time of presentation.

In this study, the authors report findings from the prospective central tumor genomic testing of samples from PROfound. Specific details about tumor sample requirements and processing were provided in the poster. Tumors were analyzed using FoundationOne based sequencing of formalin fixed and paraffin impeded tissue. Quality control showed that optimal tissue for DNA extraction was a nucleated tissue surface area of 5-7.5 square millimeters, with a minimum of 20% tumor content. A minimum of 50 ng of DNA post-extraction was required to make next generation sequencing libraries. When multiple samples were available, the largest and newest samples were utilized for the study. 84% of samples were from primary tumor tissue, with a success rate of 54% in primary tissue and 64% in metastatic tissue.

ASCOGU20_PROfound.png

Success rates also varied by sample age, tumor size, and collection method.

ASCOGU20_PROfound2.png


ASCOGU20_PROfound3.png

ASCOGU20_PROfound4.png

Presented by: Maha H.A. Hussain MD, Professor of Medicine and Deputy Director of the Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine

Written by: Alok Tewari, MD, PhD, Medical Oncology Fellow at the Dana-Farber Cancer Institute, at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California