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Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial.
Pujade-Lauraine, Eric; Ledermann, Jonathan A; Selle, Frédéric; Gebski, Val; Penson, Richard T; Oza, Amit M; Korach, Jacob; Huzarski, Tomasz; Poveda, Andrés; Pignata, Sandro; Friedlander, Michael; Colombo, Nicoletta; Harter, Philipp; Fujiwara, Keiichi; Ray-Coquard, Isabelle; Banerjee, Susana; Liu, Joyce; Lowe, Elizabeth S; Bloomfield, Ralph; Pautier, Patricia.
Afiliación
  • Pujade-Lauraine E; Medical Oncology Department, Université Paris Descartes, AP-HP, Paris, France. Electronic address: epujade@arcagy.org.
  • Ledermann JA; Department of Oncology, University College London, London, UK.
  • Selle F; Hôpital Tenon, Paris, France.
  • Gebski V; Department of Biostatistics and Research Methodology, University of Sydney, Sydney, NSW, Australia.
  • Penson RT; Department of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
  • Oza AM; Princess Margaret Cancer Centre, Toronto, Canada.
  • Korach J; Gynecologic Oncology Department, Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel.
  • Huzarski T; Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
  • Poveda A; Instituto Valenciano de Oncología, Valencia, Spain.
  • Pignata S; Istituto Tumori Pascale di Napoli, Naples, Italy.
  • Friedlander M; Department of Medical Oncology, University of New South Wales Clinical School, Prince of Wales Hospital, Randwick, NSW, Australia.
  • Colombo N; Gynecology Department, University of Milan-Bicocca and Istituto Europeo Oncología, Milan, Italy.
  • Harter P; Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany.
  • Fujiwara K; Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
  • Ray-Coquard I; Medical Oncology Department, Centre Léon Bérard and University Claude Bernard, Lyon, France.
  • Banerjee S; The Royal Marsden NHS Foundation Trust, London, UK.
  • Liu J; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Lowe ES; AstraZeneca, Gaithersburg, MD, USA.
  • Bloomfield R; AstraZeneca, Cambridge, UK.
  • Pautier P; Gustave Roussy Cancer Campus, Villejuif, France.
Lancet Oncol ; 18(9): 1274-1284, 2017 09.
Article en En | MEDLINE | ID: mdl-28754483
BACKGROUND: Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has previously shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2 (BRCA1/2) mutation using a tablet formulation of olaparib. METHODS: This international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial evaluated olaparib tablet maintenance treatment in platinum-sensitive, relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at least two lines of previous chemotherapy. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status at baseline of 0-1 and histologically confirmed, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer. Patients were randomly assigned 2:1 to olaparib (300 mg in two 150 mg tablets, twice daily) or matching placebo tablets using an interactive voice and web response system. Randomisation was stratified by response to previous platinum chemotherapy (complete vs partial) and length of platinum-free interval (6-12 months vs ≥12 months) and treatment assignment was masked for patients, those giving the interventions, data collectors, and data analysers. The primary endpoint was investigator-assessed progression-free survival and we report the primary analysis from this ongoing study. The efficacy analyses were done on the intention-to-treat population; safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01874353, and is ongoing and no longer recruiting patients. FINDINGS: Between Sept 3, 2013, and Nov 21, 2014, we enrolled 295 eligible patients who were randomly assigned to receive olaparib (n=196) or placebo (n=99). One patient in the olaparib group was randomised in error and did not receive study treatment. Investigator-assessed median progression-free survival was significantly longer with olaparib (19·1 months [95% CI 16·3-25·7]) than with placebo (5·5 months [5·2-5·8]; hazard ratio [HR] 0·30 [95% CI 0·22-0·41], p<0·0001). The most common adverse events of grade 3 or worse severity were anaemia (38 [19%] of 195 patients in the olaparib group vs two [2%] of 99 patients in the placebo group), fatigue or asthenia (eight [4%] vs two [2%]), and neutropenia (ten [5%] vs four [4%]). Serious adverse events were experienced by 35 (18%) patients in the olaparib group and eight (8%) patients in the placebo group. The most common in the olaparib group were anaemia (seven [4%] patients), abdominal pain (three [2%] patients), and intestinal obstruction (three [2%] patients). The most common in the placebo group were constipation (two [2%] patients) and intestinal obstruction (two [2%] patients). One (1%) patient in the olaparib group had a treatment-related adverse event (acute myeloid leukaemia) with an outcome of death. INTERPRETATION: Olaparib tablet maintenance treatment provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Apart from anaemia, toxicities with olaparib were low grade and manageable. FUNDING: AstraZeneca.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Ftalazinas / Piperazinas / Quimioterapia de Mantención / Antineoplásicos Tipo de estudio: Clinical_trials / Diagnostic_studies Aspecto: Patient_preference Límite: Female / Humans / Middle aged Idioma: En Revista: Lancet Oncol Asunto de la revista: NEOPLASIAS Año: 2017 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Ftalazinas / Piperazinas / Quimioterapia de Mantención / Antineoplásicos Tipo de estudio: Clinical_trials / Diagnostic_studies Aspecto: Patient_preference Límite: Female / Humans / Middle aged Idioma: En Revista: Lancet Oncol Asunto de la revista: NEOPLASIAS Año: 2017 Tipo del documento: Article Pais de publicación: Reino Unido