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ASCO 2019 Annual Meeting

ASCO 2019: Targeted Next-Generation Sequencing of Metastatic Castrate-Sensitive Prostate Cancer: A Pilot Molecular Analysis in the STAMPEDE Multi-Center Clinical Trial - Medical Oncologist Perspective

Chicago, IL (UroToday.com) STAMPEDE (Systemic Therapy in Advancing Metastatic Prostate Cancer: Evaluation of Drug Efficacy) is a novel adaptive multi-arm, multi-stage platform which has been studying men with locally advanced or metastatic prostate cancer. Several practice-changing findings have been reported through STAMPEDE, including the use of abiraterone in addition to ADT for patients with both high volume and low volume metastatic hormone-sensitive prostate cancer (mHSPC), as well as the incorporation of radiotherapy for patients with low volume disease.1, 2 This study provides the initial data regarding molecular analysis of patients with HSPC as part of the STAMPEDE cohort.

This presentation provides tissue based next-generation sequencing (NGS) data on 115 of the 186 patients enrolled so far from 15 UK centers. Baseline characteristics are shown below.

ASCO2019_Baselinecharacteristics.png

Almost all patients (97%) had metastatic disease at the time of presentation and the majority of patients had Gleason 8 or higher tumors (83%). PTEN was frequently altered, more commonly PTEN loss (25%), but PTEN mutation was also seen (9%). TP53 mutation or loss occurred in 1/3 of the patients and alterations in PI3K signaling (16%), Wnt signaling (14%), cell cycle control (6%), and DNA repair (14%) were also observed (as defined as pathogenic mutations in ATM, BRIP1, BARD1, BRCA1, BRCA2, CDK12, CHEK2, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D, and RAD54L). In this untreated setting, no patients had any androgen receptor mutations.

GenomicprofileofmCSPC.png

The study being discussed in this presentation provides valuable genomic insight into the landscape of untreated metastatic prostate cancer and demonstrates that certain genomic characteristics are quite similar in this setting to patients in the castration-resistant setting. As expected in the untreated setting, no patients had any androgen receptor mutations, which may be seen in up 20% of patients with treated prostate cancer.3 Interestingly, PTEN alterations appear to be seen in the same frequency in the untreated metastatic setting as the pre-treated metastatic setting. It was seen in about 34% of patients here and has been seen in about 32% of patients in a recently published study evaluating 3,476 advance prostate tumors. Further work should include linking this genomic data with the clinical outcomes of these patients to see if any alterations predict response or resistance to any of our current therapies.

Presented by: Clare Gilson, MD, University College London, London, England  

Written by: Jason Zhu, MD, Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 ASCO Annual Meeting #ASCO19, May 31-June 4, 2019, Chicago, IL USA

References:
  1. James ND, de Bono JS, Spears MR, et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. New England Journal of Medicine 2017;377:338-51.
  2. Parker CC, James ND, Brawley CD, et al. Radiotherapy to the primary tumor for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomized controlled phase 3 trial. The Lancet 2018;392:2353-66.
  3. Chung JH, Dewal N, Sokol E, et al. Prospective Comprehensive Genomic Profiling of Primary and Metastatic Prostate Tumors. JCO Precision Oncology, 2019.