21 november 2022: zie ook dit artikel: https://kanker-actueel.nl/NL/prostaatkankerpatienten-waarbij-dna-is-getest-via-in-bloed-circulerend-tumorweefsel-ctdna-hebben-bij-positieve-brca-1-en-2-en-atm-mutaties-meer-baat-bij-olaparib-in-vergelijking-met-enzalutamide-en-abiraterone.html

25 mei 2020: Lees ook dit artikel:

https://kanker-actueel.nl/olaparib-geeft-betere-resultaten-op-ziekteprogressievrije-tijd-en-overall-overleving-dan-enzalutamide-en-abiraterone-bij-patienten-met-uitgezaaide-hormoonresistente-prostaatkanker-met-de-juiste-dna-mutaties.html

1 april 2019: Bron: European Urology

Mannen met gevorderde uitgezaaide prostaatkanker die olaparib krijgen hebben daarvoor wel een BRCA 1 of BRCA 2 mutatie nodig blijkt uit een kleinschalige studie bij totaal 23 mannen. De mediane progressievrije ziekte bij mannen met een BRCA mutatie bleek 12,3 maanden tegenover slechts 2,4 maanden bij mannen die een ATM mutatie hadden. Het aanslaan van de behandeling blijkt bij ATM mutaties 0 procent te zijn tegenover 75 procent bij mannen met een BRCA 1 of BRCA 2 mutatie.

Het volledige studierapport: Differential Response to Olaparib Treatment Among Men with Metastatic Castration-resistant Prostate Cancer Harboring BRCA1 or BRCA2 Versus ATM Mutations is tegen betaling in te zien.

Hier het abstract van de studie:

European Urology: DOI: https://doi.org/10.1016/j.eururo.2019.02.002

Differential Response to Olaparib Treatment Among Men with Metastatic Castration-resistant Prostate Cancer Harboring BRCA1 or BRCA2 Versus ATM Mutations

Catherine H. Marshall^a

Alexandra O. Sokolova^b^,^c

Andrea L. McNatty^d

Heather H. Cheng^b^,^c

Mario A. Eisenberger^a

Alan H. Bryce^d

Michael T. Schweizer^b^,^c

Emmanuel S. Antonarakis^a^,^,

Correspondence information about the author Emmanuel S. Antonarakis

Email the author Emmanuel S. Antonarakis

Associate Editor: Todd Morgan

Statistical Editor: Andrew Vickers

Abstract

Background

Poly ADP-ribose polymerase (PARP) inhibitors, such as olaparib, are being explored as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) in men harboring mutations in homologous recombination DNA-repair genes. Whether responses to PARP inhibitors differ according to the affected gene is currently unknown.

Objective

To determine whether responses to PARP inhibitors differ between men with BRCA1/2 and those with ATM mutations.

Design, setting, and participants

This was a multicenter retrospective review of 23 consecutive men with mCRPC and pathogenic germline and/or somatic BRCA1/2 or ATM mutations treated with olaparib at three academic sites in the USA.

Outcome measurements and statistical analysis

The proportion of patients achieving a ≥50% decline in prostate-specific antigen (PSA₅₀ response) was compared using Fisher's exact test. Clinical and radiographic progression-free survival (PFS) and overall survival were estimated using Kaplan-Meier analyses and compared using the log-rank test.

Results and limitations

The study included two men with BRCA1 mutations, 15 with BRCA2 mutations, and six with ATM mutations. PSA₅₀ responses to olaparib were achieved in 76% (13/17) of men with BRCA1/2 versus 0% (0/6) of men with ATM mutations (Fisher's exact test; p = 0.002). Patients with BRCA1/2 mutations had median PFS of 12.3 mo versus 2.4 mo for those with ATM mutations (hazard ratio 0.17, 95% confidence interval 0.05–0.57; p = 0.004). Limitations include the retrospective design and relatively small sample size.

Conclusions

Men with mCRPC harboring ATM mutations experienced inferior outcomes to PARP inhibitor therapy compared to those harboring BRCA1/2 mutations. Alternative therapies should be explored for patients with ATM mutations.

Patient summary

Mutations in BRCA1/2 and ATM genes are common in metastatic prostate cancer. In this study we compared outcomes for men with BRCA1/2 mutations to those for men with ATM mutations being treated with olaparib. We found that men with ATM mutations do not respond as well as men with BRCA1/2 mutations.

olaparib, ATM mutaties, BRCA 1 en 2, progressievrije ziekte, prostaatkanker