Zie in gerelateerde artikelen meer artikelen over parpremmers bij eierstokkanker

3 februari 2025: Bron: Annals of Oncology

Uit de resultaten van de fase IIIb studie OReO blijkt dat bij patiënten met gevorderde epitheliaal eierstokkanker  die gevoelig bleken voor op platina gebaseerde chemo een op herhaling gebaseerde onderhoudsbehandeling met parpremmer olaparib alsnog effectief. Ongeacht de BRCA 1/2 status. 

De OReO studie is een gerandomiseerde placebo gecontroleerde fase IIIb studie verdeeld in twee onderzoeksgroepen, te weten een groep patiënten met gevorderde eierstokkanker die eerder gevoelig bleken voor platinum chemotherapie en met BRCA 1 en 2 mutatie en een groep patiënten zonder BRCA 1 en 2 mutatie en ter vergelijking voor beide groepen een placebogroep. 

De 1-jaars ziekteprogressievrije tijd blijkt voor de patiënten uit de BRCA 1 / 2 groep 19 procent en voor de niet BRCA 1/2 groep 14 procent in vergelijking met 0 procent voor de placebogroepen in beide groepen.


De resultaten uit het abstract vertaald in het Nederlands:

  • 74 patiënten in de BRCA-gemuteerde groep werden gerandomiseerd naar olaparib en 38 naar placebo, en 72 patiënten in de niet-BRCA-gemuteerde groep werden gerandomiseerd naar olaparib en 36 naar placebo;
  • Meer dan 85% van de patiënten in beide groepen had ≥3 eerdere chemotherapie kuren gekregen.
  • In de BRCA-gemuteerde groep was de mediane progressievrije ziekte (PFS) 4,3 maanden met olaparib versus 2,8 maanden met placebo [gevarenratio (HR) 0,57; 95% betrouwbaarheidsinterval (BI) 0,37-0,87; P = 0,022];
  • 1-jaars PFS-percentages waren 19% versus 0% (Kaplan-Meier-schattingen) in vergelijking met placebogroep.
  • In de niet-BRCA-gemuteerde groep was de mediane progressievrije ziekte (PFS) 5,3 maanden voor olaparib versus 2,8 maanden voor placebogroep (HR 0,43; 95% BI 0,26-0,71; P = 0,0023);
  • 1-jaars PFS-percentages waren 14% versus 0% (Kaplan-Meier-schattingen) voor de placebogroep.
Zie Table 1 voor karakteristieken van de deelnemende patiënten.

Het volledige studierapport is gratis in te zien. Klik daarvoor op de titel van het abstract:

Annals of Oncology

Volume 34, Issue 12, December 2023, Pages 1152-1164
Annals of Oncology
Original article

Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial

https://doi.org/10.1016/j.annonc.2023.09.3110Get rights and content
Under a Creative Commons license
open access

Highlights

  • •
    OReO is the first study to show that maintenance olaparib rechallenge provides a PFS benefit in relapsed ovarian cancer.
  • •
    Statistically significant PFS benefit is seen with olaparib rechallenge over placebo independent of BRCA mutation status.
  • •
    A proportion of the OReO population was still progression free at 1 year.
  • •
    No new safety signals were observed with maintenance olaparib rechallenge.
  • •
    Further investigation may reveal identifiable characteristics of those patients deriving the most clinical benefit.

Background

Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the standard of care for some patients with advanced ovarian cancer. We evaluated the efficacy and safety of PARP inhibitor rechallenge.

Patients and methods

This randomized, double-blind, multicenter trial (NCT03106987) enrolled patients with platinum-sensitive relapsed ovarian cancer who had received one prior PARP inhibitor therapy for ≥18 and ≥12 months in the BRCA-mutated and non-BRCA-mutated cohorts, respectively, following first-line chemotherapy or for ≥12 and ≥6 months, respectively, following a second or subsequent line of chemotherapy. Patients were in response following their last platinum-based chemotherapy regimen and were randomized 2 : 1 to maintenance olaparib tablets 300 mg twice daily or placebo. Investigator-assessed progression-free survival (PFS) was the primary endpoint.

Results

Seventy four patients in the BRCA-mutated cohort were randomized to olaparib and 38 to placebo, and 72 patients in the non-BRCA-mutated cohort were randomized to olaparib and 36 to placebo; >85% of patients in both cohorts had received ≥3 prior lines of chemotherapy. In the BRCA-mutated cohort, the median PFS was 4.3 months with olaparib versus 2.8 months with placebo [hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.37-0.87; P = 0.022]; 1-year PFS rates were 19% versus 0% (Kaplan–Meier estimates). In the non-BRCA-mutated cohort, median PFS was 5.3 months for olaparib versus 2.8 months for placebo (HR 0.43; 95% CI 0.26-0.71; P = 0.0023); 1-year PFS rates were 14% versus 0% (Kaplan–Meier estimates). No new safety signals were identified with olaparib rechallenge.

Conclusions

In ovarian cancer patients previously treated with one prior PARP inhibitor and at least two lines of platinum-based chemotherapy, maintenance olaparib rechallenge provided a statistically significant, albeit modest, PFS improvement over placebo in both the BRCA-mutated and non-BRCA-mutated cohorts, with a proportion of patients in the maintenance olaparib rechallenge arm of both cohorts remaining progression free at 1 year.

Acknowledgements

We thank Dr Mansoor R. Mirza for his contribution on the steering committee; the members of the independent data monitoring committee, Dr Christian Marth, Dr Nicholas Reed, and Dr Xavier Paoletti; and Alan Barnicle (AstraZeneca), Zahid Bashir (AstraZeneca), Steven Radziwonik (AstraZeneca), Rosie Taylor (AstraZeneca), Steve Keefe (Merck & Co., Inc.), and Myriad Genetic Laboratories, Inc. for their contribution to this trial.
Medical writing assistance was provided by Gillian Keating MBChB, of Cence, funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

This work was funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (no grant number).


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Data Sharing

Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data-sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Data for studies directly listed on Vivli can be requested through Vivli at www.vivli.org. Data for studies not listed on Vivli could be requested through Vivli at https://vivli.org/members/enquiries-about-studies-not-listed-on-the-vivli-platform/. AstraZeneca Vivli member page is also available outlining further details: https://vivli.org/ourmember/astrazeneca/.

Supplementary data

Supplementary Material

References






eierstokkanker, parpremmers, olaparib, chemo, ziekteprogressievrije tijd, chemo gevoelig, recidief


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