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Titel:

Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer.

Dokumenttyp:
Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
Autor(en):
Ray-Coquard, Isabelle; Pautier, Patricia; Pignata, Sandro; Pérol, David; González-Martín, Antonio; Berger, Regina; Fujiwara, Keiichi; Vergote, Ignace; Colombo, Nicoletta; Mäenpää, Johanna; Selle, Frédéric; Sehouli, Jalid; Lorusso, Domenica; Guerra Alía, Eva M; Reinthaller, Alexander; Nagao, Shoji; Lefeuvre-Plesse, Claudia; Canzler, Ulrich; Scambia, Giovanni; Lortholary, Alain; Marmé, Frederik; Combe, Pierre; de Gregorio, Nikolaus; Rodrigues, Manuel; Buderath, Paul; Dubot, Coraline; Burges, Alexa...     »
Abstract:
BACKGROUND: Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown. METHODS: We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum-taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or BRCA mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death. RESULTS: Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. CONCLUSIONS: In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation. (Funded by ARCAGY Research and others; PAOLA-1 ClinicalTrials.gov number, NCT02477644.).
Zeitschriftentitel:
N Engl J Med
Jahr:
2019
Band / Volume:
381
Heft / Issue:
25
Seitenangaben Beitrag:
2416-2428
Volltext / DOI:
doi:10.1056/NEJMoa1911361
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/31851799
Print-ISSN:
0028-4793
TUM Einrichtung:
Frauenklinik und Poliklinik
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