Maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer: Outcomes by somatic and germline BRCA and other homologous recombination repair gene mutation status in the ORZORA trial
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu multicentrická studie, časopisecké články, práce podpořená grantem
PubMed
37030280
DOI
10.1016/j.ygyno.2023.03.019
PII: S0090-8258(23)00166-X
Knihovny.cz E-zdroje
- Klíčová slova
- BRCA mutation, HRR, Maintenance, Olaparib, Ovarian cancer,
- MeSH
- epiteliální ovariální karcinom farmakoterapie genetika MeSH
- ftalaziny škodlivé účinky MeSH
- kvalita života MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie genetika MeSH
- mutace MeSH
- nádory vaječníků * farmakoterapie genetika patologie MeSH
- prospektivní studie MeSH
- protinádorové látky * terapeutické užití MeSH
- rekombinační oprava DNA MeSH
- zárodečné mutace MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ftalaziny MeSH
- olaparib MeSH Prohlížeč
- protinádorové látky * MeSH
BACKGROUND: The open-label, single-arm, multicenter ORZORA trial (NCT02476968) evaluated the efficacy and safety of maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) who had tumor BRCA mutations (BRCAm) of germline (g) or somatic (s) origin or non-BRCA homologous recombination repair mutations (HRRm) and were in response to their most recent platinum-based chemotherapy after ≥2 lines of treatment. METHODS: Patients received maintenance olaparib capsules (400 mg twice daily) until disease progression. Prospective central testing at screening determined tumor BRCAm status and subsequent testing determined gBRCAm or sBRCAm status. Patients with predefined non-BRCA HRRm were assigned to an exploratory cohort. The co-primary endpoints were investigator-assessed progression-free survival (PFS; modified Response Evaluation Criteria in Solid Tumors v1.1) in BRCAm and sBRCAm cohorts. Secondary endpoints included health-related quality of life (HRQoL) and tolerability. RESULTS: 177 patients received olaparib. At the primary data cut-off (17 April 2020), the median follow-up for PFS in the BRCAm cohort was 22.3 months. The median PFS (95% CI) in BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts was 18.0 (14.3-22.1), 16.6 (12.4-22.2), 19.3 (14.3-27.6) and 16.4 (10.9-19.3) months, respectively. Most patients with BRCAm reported improvements (21.8%) or no change (68.7%) in HRQoL and the safety profile was as expected. CONCLUSIONS: Maintenance olaparib had similar clinical activity in PSR OC patients with sBRCAm and those with any BRCAm. Activity was also observed in patients with a non-BRCA HRRm. ORZORA further supports use of maintenance olaparib in all patients with BRCA-mutated, including sBRCA-mutated, PSR OC.
Beatson West of Scotland Cancer Centre and University of Glasgow Glasgow UK
Department of Oncology University of Turin At Mauriziano Hospital Turin Italy
General University Hospital Prague 1st Faculty of Medicine Charles University Prague Czech Republic
Guy's and St Thomas' NHS Foundation Trust London UK
Hospital Universitario Miguel Servet Zaragoza Spain
ICO Badalona Hospital Universitari Germans Trias i Pujol Barcelona Spain
ICO l'Hospitalet Hospital Duran i Reynals L'Hospitalet de Llobregat Barcelona Spain
Istituto Nazionale Tumori 'Fondazione G Pascale' IRCCS Napoli Italy
Medical University Karol Marcinkowski Poznań Poland
MHAT 'Central Onco Hospital' OOD Plovdiv Bulgaria
MHAT for Women's Health Nadezhda OOD Sofia Bulgaria
National Institute of Cancer Budapest Hungary
Princess Margaret Cancer Centre Toronto Ontario Canada
St James's University Hospital Leeds UK
The Christie NHS Foundation Trust and University of Manchester Manchester UK
University Hospital Ostrava Faculty of Medicine University of Ostrava Ostrava Czech Republic
University of Milan Bicocca and European Institute of Oncology IRCCS Milan Italy
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