Durable benefit from poly(ADP-ribose) polymerase inhibitors in metastatic prostate cancer in routine practice: biomarker associations and implications for optimal clinical next-generation sequencing testing.

Autor:	Triner D; Department of Urology, Michigan Medicine, Ann Arbor, USA., Graf RP; Foundation Medicine, Cambridge, USA., Madison RW; Foundation Medicine, Cambridge, USA., Gjoerup O; Foundation Medicine, Cambridge, USA., Tukachinsky H; Foundation Medicine, Cambridge, USA., Ross JS; Foundation Medicine, Cambridge, USA; Department of Pathology, Upstate Medical University, Syracuse, USA; Department of Urology, Upstate Medical University, Syracuse, USA; Department of Medicine (Oncology), Upstate Medical University, Syracuse, USA., Quintanilha JCF; Foundation Medicine, Cambridge, USA., Li G; Foundation Medicine, Cambridge, USA., Cheng HH; University of Washington, Fred Hutchinson Cancer Center, Seattle, USA., Pritchard CC; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, USA., Zurita AJ; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA., Qin Q; Division of Hematology and Oncology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, USA., Zhang T; Division of Hematology and Oncology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, USA., Agarwal N; Department of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, USA., Reichert ZR; Department of Hematology/Oncology, University of Michigan, Ann Arbor, USA., Mateo J; Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Barcelona Hospital Campus, Barcelona, Spain., Cieslik M; Department of Pathology, University of Michigan, Ann Arbor, USA., Morgan TM; Department of Urology, Michigan Medicine, Ann Arbor, USA. Electronic address: tomorgan@med.umich.edu.
Jazyk:	angličtina
Zdroj:	ESMO open [ESMO Open] 2024 Sep; Vol. 9 (9), pp. 103684. Date of Electronic Publication: 2024 Sep 09.
DOI:	10.1016/j.esmoop.2024.103684
Abstrakt:	Background: Controlled trials have consistently demonstrated the efficacy of poly(ADP-ribose) polymerase inhibitors (PARPis) in patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1 or BRCA2 alterations (BRCAalt). However, the reported efficacy of PARPi for alterations in other homologous recombination repair (HRR) genes is less consistent. We sought to evaluate the routine practice effectiveness of PARPi between and within these groups. Design: Patient-level data from a deidentified nationwide (USA-based) cancer clinico-genomic database between January 2011 and September 2023 were extracted. Patients with mCRPC and comprehensive genomic profiling by liquid biopsy [circulating tumor DNA (ctDNA)] or tissue (tumor) biopsy and who received single-agent PARPi were included and grouped by BRCAalt, ATMalt, other HRR, or no HRR. We further subcategorized BRCAalt into homozygous loss (BRCAloss) and all other deleterious BRCAalt (otherBRCAalt). Results: A total of 445 patients met inclusion criteria: 214 with tumor and 231 with ctDNA. BRCAalt had more favorable outcomes to PARPi compared with ATM, other HRR, and no HRR groups. Within the BRCAalt subgroup, compared with other BRCAalt, BRCAloss had a more favorable time to next treatment (median 9 versus 19.4 months, P = 0.005), time to treatment discontinuation (median 8 versus 14 months, P = 0.006), and routine practice overall survival (median 14.7 versus 19.4 months, P = 0.016). Tumor BRCAloss prevalence (3.1%) was similar to ctDNA prevalence in liquid biopsy specimens with high tumor fraction (>20%). BRCAloss was not detected in orthogonal germline testing. Conclusions: PARPi routine practice effectiveness between groups mirrors prospective trials. Within the BRCAalt group, BRCAloss had the best outcomes. Unless the ctDNA tumor fraction is very high, somatic tissue testing (archival or metastatic) should be prioritized to identify patients who may benefit most from PARPi. When tissue testing is not clinically feasible, sufficient ctDNA tumor fraction levels for detection are enriched at clinical timepoints associated with tumor progression. (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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