Abstract 641P
Background
Molecular testing for homologous recombination repair (HRR) gene alterations was included in the mCRPC NCCN guidelines in 2017. Olaparib, a PARP inhibitor (PARPi) for the treatment of HRR-mutated (HRRm) mCRPC was included in the NCCN guidelines in 2020 and is currently awaiting FDA approval. We assessed HRRm testing in mCRPC pts prior to PARPi approval.
Methods
Pts with adenocarcinoma mCRPC diagnosis (dx) were identified in the US Flatiron Health EHR-derived de-identified database (01/2013–03/2019), which includes 91% pts from community-based clinical practices and 9% from academic settings. Patterns of HRRm testing for 6 HRR gene alterations (ATM, BRCA1/2, CDK12, PALB2, FANCA) were described overall and stratified by year. Prevalence of specific gene alterations was analysed.
Results
Of 5,213 pts (mean age: 73 yrs; mean follow-up post-mCRPC dx: 1.5 yrs), 674 (13%) had a documented testing for ≥1 of the 6 HRRm pre- or post-mCRPC dx. The proportion of pts tested post-mCRPC dx for the 6 HRRm increased from 0% in 2013 to 11% in 2018 (Table). BRCA1/2 was assessed in 97% of pts vs ATM 86%; PALB2 66%; CDK12 43%; and FANCA 41%. The prevalence of specific HRRm, measured as a proportion of those tested for each HRRm, was 1% for FANCA, 2% for PALB2, 3% for BRCA1, 6% for ATM, 7% for CDK12, and 13% for BRCA2 (24% for any of the 6 HRRm). Overall, 346 (51%) pts had ≥1 germline test and 359 (53%) ≥1 tumor test, respectively. A germline alteration for ≥1 of the 6 HRRm was found in 60/346 (17%) pts. Of 286/346 pts without germline alteration, 36/286 (13%) subsequently had a tumor test of which 5/36 (14%) had a gene alteration. Table. Cross-Sectional HRRm Testing Patterns. Table: 641P
| Year | ||||||
| 2013 | 2014 | 2015 | 2016 | 2017 | 2018 | |
| Pts with mCRPC dx†, n | 413 | 1,181 | 1,888 | 2,442 | 2,864 | 2,883 |
| Pts with HRRm test, n (% pts with mCRPC dx) | 1 (0.2) | 15 (1.2) | 46 (2.4) | 77 (3.1) | 180 (6.3) | 313 (10.9) |
| __Pre-mCRPC dx | 0 (0) | 5 (0.4) | 9 (0.5) | 17 (0.7) | 24 (0.8) | 26 (0.9) |
| __Post-mCRPC dx | 1 (0.2) | 10 (0.8) | 39 (2.1) | 60 (2.4) | 158 (5.5) | 289 (10.0) |
| ____Germline only‡ | 0 (0) | 2 (0.2) | 19 (1.0) | 16 (0.7) | 60 (2.1) | 137 (4.8) |
| ____Tumor only‡ | 1 (0.2) | 7 (0.6) | 18 (1.0) | 34 (1.4) | 81 (2.8) | 116 (4.0) |
| ____Both ‡ | 0 (0) | 0 (0) | 2 (0.1) | 8 (0.3) | 8 (0.3) | 20 (0.7) |
† mCRPC dx was before or during the yr‡ Excl. 33 pts with unspecified type
Conclusions
This US real-world study primarily in community settings showed low HRRm testing rates in mCRPC pts, with a modest increase after 2017. In line with published data, germline testing did not identify all HRRm. With a shift in access to PARP inhibitors, efforts are needed to support awareness and access to HRRm testig for pts with mCRPC.
Clinical trial identification
Editorial acknowledgement
Editorial assistance was provided by Mona Lisa Chanda, an employee of Analysis Group, Inc. in Montréal, Quebec, Canada.
Legal entity responsible for the study
Merck & Co., Inc. and Analysis Group, Inc.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and AstraZeneca.
Disclosure
N. Shore: Speaker Bureau/Expert testimony: Astellas, Bayer, Janssen; Leadership role: LUGPA, BCAN Boards; Research grant/Funding (institution): Astellas, Bayer, Tolmar; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer, BMS ,Dendreon,Fergene, Ferring, Janssen, Merck, Myovant, Nymox, Pfizer, Sanofi, Tolmar, Astellas, Amgen, AstraZeneca. R. Ionescu-Ittu: Research grant/Funding (institution): Employed at Analysis Group, a company that has received funding from Merck & Co, Inc.; Full/Part-time employment: Analysis Group has provided paid consulting services to various clients in the bio-medical arena. L. Yang: Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. F. Laliberté: Research grant/Funding (institution): Employed at Analysis Group, a company that has received funding from Merck: Merck & Co, Inc.; Full/Part-time employment, Analysis Group has provided paid consulting services to various clients in the bio-medical arena. S. Payne: Full/Part-time employment: AstraZeneca. A. Gayle: Full/Part-time employment: AstraZeneca. S. Amin: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. M. Mahendran: Research grant/Funding (institution): Employed at Analysis Group, a company that has received funding from Merck: Merck; Full/Part-time employment, Analysis Group has provided paid consulting services to various clients in the bio-medical arena. D. Lejeune: Research grant/Funding (institution): Employed at Analysis Group, a company that has received funding from Merck: Merck; Full/Part-time employment, Analysis Group has provided paid consulting services to various clients in the bio-medical arena. L. Yu: Research grant/Funding (institution): Employed at Analysis Group, a company that has received funding from Merck: Merck; Full/Part-time employment, Analysis Group has provided paid consulting services to various clients in the bio-medical arena. J. Burgents: Shareholder/Stockholder/Stock options, Full/Part-time employment, Spouse/Financial dependant, Stock options and spouse: Merck & Co, Inc. M.S. Duh: Research grant/Funding (institution): Employed at Analysis Group, a company that has received funding from Merck: Merck; Full/Part-time employment, Analysis Group has provided paid consulting services to various clients in the bio-medical arena. S. Ghate: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck Sharp & Dohme Corp.