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E-Poster Display

654P - Real-world treatment (Tx) patterns in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair mutations (HRRm+)

Date

17 Sep 2020

Session

E-Poster Display

Topics

Tumour Site

Prostate Cancer

Presenters

Neal Shore

Citation

Annals of Oncology (2020) 31 (suppl_4): S507-S549. 10.1016/annonc/annonc275

Authors

N. Shore1, R. Ionescu-Ittu2, F. Laliberté2, L. Yang3, A. Gayle4, S. Payne5, M. Mahendran2, S. Amin6, D. Lejeune7, J.E. Burgents8, M.S. Duh9, L. Yu9, S. Ghate10

Author affiliations

  • 1 Urology, Carolina Urologic Research Center, 29572 - Myrtle Beach/US
  • 2 Healthcare, Groupe d’analyse, Ltée, H3B 0G7 - Montréal/CA
  • 3 Center For Observational And Real-world Evidence, Merck, 07033 - Kenilworth/US
  • 4 Epidemiology, AstraZeneca, CB2 0AA - Cambridge/GB
  • 5 Senior Global Medical Affairs Leader, Head Of Gu Cancers, AstraZeneca, CB2 0AA - Cambridge/GB
  • 6 Health Economics And Outcomes Research, AstraZeneca, 20878 - Gaithersberg/US
  • 7 Healthcare, Groupe d'analyse, Ltée, H3B 0G7 - Montréal/CA
  • 8 Global Cinical Deveopment, Merck & Co., Inc., 07033 - Kenilworth/US
  • 9 Healthcare, Analysis Group, Inc., 02199 - Boston/US
  • 10 Center For Observational & Real World Evidence, Merck & Co., Inc., 07033 - Kenilworth/US

Resources

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Abstract 654P

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

% Median months on tx
Pts with ≥ 1 LOT (N = 151) On 1L
1L class
NHA 54 5.5
Chemo 19 2.9
I/O 11 3.5
Other 8 2.1
Combinations of classes 8 5.2
NHA-based 7 5.3
Pts with ≥ 2 LOTs (N = 121) From 1L start to 2L end
1L → 2L (by frequency)
NHA → NHA 20 15.9
NHA → Chemo 14 9.8
NHA → Other 12 8.6
Remaining 15 sequences 54 9.4
Pts with ≥ 3 LOTs (N = 94) From 1L start to 3L end
1L → 2L → 3L (by frequency)
NHA → NHA → Chemo 12 19.3
I/O → NHA → NHA 7 20.4
NHA → NHA → Other 6 27.8
Remaining 32 sequences 75 14.4

I/O , immunotherapy (excl. pembrolizumab); NHA , new hormonal agents (e.g., abiraterone, enzalutamide); Other , incl. pembrolizumab, targeted tx, radium-223, androgren-deprivation tx, clinical trial tx.

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.

Clinical trial identification

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.

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