(UroToday.com) The 2022 GU ASCO Annual meeting included a prostate cancer session featuring work from Dr. Iris Kloots and investigators presenting the first results of the PROMPT trial, precision oncology allocation in patients with early castration-resistant prostate cancer (CRPC) following routine molecular profiling. Radboudumc, a tertiary referral center for prostate cancer, hosts a molecular tumor board, and frequently sees CRPC patients for referral for genetic testing. In the period 2017-2020, almost 50% of heavily pre-treated CRPC patients received a recommendation for a genetically matched therapy. In 2020, Dr. Kloots and colleagues initiated the PROMPT trial (NCT04746300) to prospectively study the impact of routine early molecular characterization in CRPC. Increased genetically matched therapy utilization of targeted- and immunotherapy may improve the outcome and quality of life of patients with metastatic CRPC, and lead to lower medical resource utilization. At GU ASCO 2022, Dr. Kloots reported the first results from this observational trial.
Within the PROMPT trial, prior to receiving first- or second line standard of care CRPC therapy, up to 300 patients were offered molecular tumor characterization with the TruSightOncology 500 panel (TSO500). Formalin-fixed paraffin-embedded prostate or metastatic tissue biopsies were used, preferably newly obtained. To assess both mutations and copy number alterations, the TSO500 required a minimal tumor cell percentage of 30%. Results were discussed within the Radboudumc molecular tumor board for genetically matched therapy recommendations. Actionable targets were defined per Precision Medicine Working group criteria and, when druggable, within the Drug Rediscovery Protocol trial (NCT02925234). All patients with tumor mutations carrying with it a risk for cancer predisposition were referred for genetic counseling. Follow-up with patient-reported outcomes (EORTC QLQ-C30, EQ5D, BPI & EPIC-26 questionnaires) and medical resource utilization was conducted every 3 months until withdrawal or death. The study schema is as follows:
From February 2020 until October 2021 the study included 284 consecutive CRPC patients with a median age of 70 years (range 46-86) with a median follow-up of 6.8 months. Newly obtained biopsies and archival material were used in 131 and 126 patients, respectively. Median tumor cell percentage was 60% (range: 20-90%). TSO500 results could be reported in 254 (89%) cases, with at least one putative clinically relevant aberration in 188 evaluable patients (74%). In 100 patients (39,4%) ≥ 1 druggable target was found, with the most common actionable alterations in PTEN (19%), BRCA2 (9%) or in mismatch-repair genes or resulting in high tumor mutational burden (5%). Out of the 100 druggable patients, 31 patients (31%) initiated a form of genetically matched therapy, 4 patients (4%; 2 BRCA2, 2 PTEN) died prior to receiving genetically matched therapy, in 65 patients (65%) genetically matched therapy is pending as they receive standard of care.
Dr. Kloots concluded this presentation of the final results of the PROMPT trial with the following summary statements:
- Routine molecular profiling early in the CRPC setting is feasible in a tertiary referral center with a molecular tumor board and high volume of CRPC patients
- Almost 40% CRPC patients harbored an actionable target with 31% of these patients already allocated to a genetically matched therapy
- Failure rates of NGS were low at 11%
Presented by: Iris S. H. Kloots, Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands
Co-Authors: Peter H.J. Slootbeek, Minke Smits, Sjoerd van Helvert, Leonie I. Kroeze, Marleen Kets, Katrien Grünberg, Jolique van Ipenburg, Marjolijn Ligtenberg, Jack Schalken, Inge M. van Oort, Haiko Bloemendal, Winald R. Gerritsen, Niven Mehra
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022