(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on prostate cancer, and a presentation by Dr. Arshit Narang discussing the impact of alterations in tumor suppressor genes on survival outcomes in patients with de novo metastatic castration-sensitive prostate cancer (CSPC) receiving ADT with androgen receptor pathway inhibition or docetaxel.
Tumor suppressor gene alterations have been associated with poor survival in the mCRPC setting and in the mCSPC setting from small single institution cohorts.1,2 However, large studies evaluating their impact on survival outcomes with ADT intensification in mCSPC settings are lacking. At the 2024 ASCO annual meeting, Dr. Narang and colleagues evaluated the impact of tumor suppressor gene alterations on outcomes in a large real-world patient population with de novo-mCSPC receiving ADT treatment with androgen receptor pathway inhibition or docetaxel.
This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine Prostate Cancer clinical-genomic database (FH-FMI CGDB), with de-identified data originating from approximately 800 US cancer clinics. Inclusion criteria included de novo-mCSPC, tissue biopsy within 90 days of diagnosis, and initiation of androgen receptor pathway inhibition or docetaxel + ADT within 120 days of diagnosis. Time to castration-resistance and overall survival, indexed from metastatic diagnosis, were evaluated with Cox proportional hazards models adjusted for baseline prognostic factors (PSA, Gleason score, age, ECOG, hemoglobin, alkaline phosphatase, and albumin). Overall survival risk intervals were left truncated to date of comprehensive genomic profiling report to adjust for immortal time bias.
Of 5,356 patients in FH-FMI CGDB, 571 met inclusion criteria. Among these patient, 321 received ADT + androgen receptor pathway inhibition and 250 ADT + docetaxel. Patients with pathogenic tumor suppressor gene alterations were: 214 TP53 (37%), 154 PTEN (27%), and 37 RB1 (6%). The baseline characteristics of the patients are summarized as follows:
The following figure summarizes the treatment class-specific outcomes of biomarker-selected groups:
Outcomes of time to castration resistance and overall survival by treatment class stratified by the presence of RB1 status is highlighted below:
The following figure summarizes the outcomes of time to castration resistance and overall survival by treatment class stratified by the presence of TP53 status:
Dr. Narang concluded his presentation discussing the impact of alterations in tumor suppressor genes on survival outcomes in patients with de novo metastatic CSPC receiving ADT with androgen receptor pathway inhibition or docetaxel with the following take-home messages:
- In this real-world analysis, altRB1 and altTP53 had worse overall survival than their respective wild-type counterparts with both androgen receptor pathway inhibition and docetaxel whereas altPTEN had similar overall survival with androgen receptor pathway inhibition and Docetaxel in de novo-mCSPC patients
- Based on these results, RB1 and TP53 may represent prognostic biomarkers guiding treatment selection and clinical trial enrollment in de novo-mCSPC and may assist with counseling and prognostication
Presented by: Arshit Narang, GU Cancer Research Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, May 31 – Tues, June 4, 2024.
References:
- Abida W, Cyrta J, Heller G, et al. Genomic correlates of clinical outcome in advanced prostate cancer. Proc Natl Acad Sci USA. 2019 Jun 4;116(23):11428-11436.
- Velez MG, Kosiorek HE, Egan JE, et al. Differential impact of tumor suppressor gene (TP53, PTEN, RB1) alterations and treatment outcomes in metastatic, hormone sensitivity prostate cancer. Prostate Cancer Prostatic Dis. 2022 Sep;25(3):479-483.