Background

The 2020 NCCN guidelines recommend olaparib, a PARP inhibitor (PARPi) currently awaiting FDA approval, for the treatment of HRRm+ mCRPC. We describe tx patterns of mCRPC pts who tested positive for ≥1 of six a priori selected HRRm (ATM, BRCA1/2, CDK12, PALB2, FANCA) before PARPi approval.

Methods

mCRPC pts with confirmed adenocarcinoma diagnosis (dx) and documented HRRm were identified in the US Flatiron Health EHR-derived deidentified database (01/2013–03/2019; 82.5% and 17.5% of pts with HRRm mCRPC in community and academic settings, respectively). Pts were followed from mCRPC dx to the end of clinical activity/data availability or death. Tx patterns (incl. tx per lines of therapies [LOTs], LOT sequences and time on tx) were described.

Results

Of 160 pts with HRRm mCRPC (mean age: 68 yrs; mean follow-up post-mCRPC: 2.1 yrs), 151 (94%) were treated with ≥ 1 LOT (121 [76%], 94 [59%], 60 [38%], and 41 [26%] with ≥ 2, ≥ 3, ≥ 4, and ≥ 5 LOTs, respectively) during follow-up. The main tx class used in 1L was new hormonal agent (NHA; 54%; Table). The most commonly selected first line (1L) tx were abiraterone (29% of pts with 1L; observed median tx duration: 4.5 mo), enzalutamide (24%; 6.1 mo), docetaxel (17%; 3.5 mo); for 2L were enzalutamide (23% of pts with 2L; 5.7 mo), abiraterone (16%; 5.7 mo), docetaxel (15%; 3.5 mo); for 3L were docetaxel (16% of pts with 3L; 3.6 mo), abiraterone (15%; 2.9 mo), enzalutamide (13%; 3.5 mo). There was a plethora of LOT sequences (Table). In pts with ≥ 2 LOTs, the most common LOT sequence by class was 1L NHA → 2L NHA (20%; median 15.9 mo from 1L start to 2L end; Table); in pts with ≥ 3 LOTs, it was 1L NHA → 2L NHA→ 3L Chemo (12%; median 19.3 mo from 1L start to 3L end). Table: 654P

LOTs by Tx Class

Conclusions

This real-world study identified poor outcomes on standard of care tx for HRRm+ mCRPC pts. The study also illustrates the lack of tx harmonization for these pts with known poor prognosis, suggesting a need for future tx optimization.

Editorial acknowledgement

Editorial assistance was provided by Mona Lisa Chanda, an employee at Analysis Group in Montréal, Quebec, Canada.

Legal entity responsible for the study

Merck & Co., Inc. and Analysis Group, Inc.

Funding

This study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and by AstraZeneca.

Disclosure

N. Shore: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen, Astellas, AstraZeneca, Bayer, BMS, Dendreon, Fergene, Ferring, Janssen, Merck, Myovant, Nymox, Pfizer, Sanofi, Tolmar; Speaker Bureau/Expert testimony: Astellas, Bayer, Janssen; Leadership role: LUGPA, BCAN Boards; Research grant/Funding (institution): Astellas, Bayer, Tolmar. R. Ionescu-Ittu: Research grant/Funding (institution), I am an employee of Analysis Group, a consulting company which has received funding from Merck: Merck & Co, Inc.; Full/Part-time employment, Analysis Group has provided paid consulting services to various clients in the biomedical arena: Analysis Group, Inc. F. Laliberté: Research grant/Funding (institution), I am an employee of Analysis Group, a consulting company which has received funding from Merck: Merck & Co, Inc.; Full/Part-time employment, Analysis Group has provided paid consulting services to various clients in the biomedical arena: Analysis Group, Inc. L. Yang: Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co, Inc. A. Gayle: Full/Part-time employment: AstraZeneca. S. Payne: Full/Part-time employment, Full-time employee: AstraZeneca. M. Mahendran: Research grant/Funding (institution), I am an employee of Analysis Group, a consulting company which has received funding from Merck: Merck & Co, Inc.; Full/Part-time employment, Analysis Group has provided paid consulting services to various clients in the biomedical arena: Analysis Group, Inc. S. Amin: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. D. Lejeune: Research grant/Funding (institution), I am an employee of Analysis Group, a consulting company which has received funding from Merck: Merck & Co, Inc.; Full/Part-time employment, Analysis Group has provided paid consulting services to various clients in the biomedical arena: Analysis Group, Inc. J.E. Burgents: Shareholder/Stockholder/Stock options, Full/Part-time employment, Spouse/Financial dependant, Regarding spouse/financial dependent, my wife works at Merck: Merck & Co, Inc. M.S. Duh: Research grant/Funding (institution), I am an employee of Analysis Group, a consulting company which has received funding from Merck: Merck & Co, Inc.; Full/Part-time employment, Analysis Group has provided paid consulting services to various clients in the biomedical arena: Analysis Group, Inc. L. Yu: Research grant/Funding (institution), I am an employee of Analysis Group, a consulting company which has received funding from Merck: Merck & Co, Inc.; Full/Part-time employment, Analysis Group has provided paid consulting services to various clients in the biomedical arena: Analysis Group, Inc. S. Ghate: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.