Academic Journal
Maintenance Olaparib for Germline BRCA -Mutated Metastatic Pancreatic Cancer
| Title: | Maintenance Olaparib for Germline BRCA -Mutated Metastatic Pancreatic Cancer |
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| Authors: | Anke Reinacher-Schick, Talia Golan, Joon Oh Park, Dirk Arnold, Do Youn Oh, Pascal Hammel, Giampaolo Tortora, Michele Reni, Hedy L. Kindler, Katia Schlienger, Michael J. Hall, Eileen M. O'Reilly, Eric Van Cutsem, David McGuinness, Gershon Y. Locker, Teresa Macarulla, Daniel Hochhauser, Hana Algül, Karen Y. Cui |
| Contributors: | [Golan T] Oncology Institute, Sheba Medical Center, Tel Aviv, Israel. Tel Aviv University, Tel Aviv, Israel. [Hammel P] Hôpital Beaujon (Assistance Publique–Hopitaux de Paris), Clichy, France. University Paris VII, Paris, France. [Reni M] IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy. [Van Cutsem E] University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium. [Macarulla T ] Hospital Universitari Vall d’Hebron , Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Hall MJ] Fox Chase Cancer Center, Philadelphia, USA., Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus |
| Source: | Scientia Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) Recercat. Dipósit de la Recerca de Catalunya instname Scientia. Dipòsit d'Informació Digital del Departament de Salut |
| Publisher Information: | Massachusetts Medical Society, 2019. |
| Publication Year: | 2019 |
| Subject Terms: | PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation::Germ-Line Mutation, fenómenos genéticos::variación genética::mutación::mutación de la línea germinal [FENÓMENOS Y PROCESOS], Adult, Male, 0301 basic medicine, Genes, BRCA2, Genes, BRCA1, Antineoplastic Agents, Kaplan-Meier Estimate, Adenocarcinoma, Digestive System Diseases::Digestive System Neoplasms::Digestive System Diseases::Pancreatic Neoplasms [DISEASES], Genetic Phenomena::Genetic Variation::Mutation::Germ-Line Mutation [PHENOMENA AND PROCESSES], Piperazines, Medicaments antineoplàstics, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Humans, ENFERMEDADES::enfermedades del sistema digestivo::neoplasias del sistema digestivo::enfermedades del sistema digestivo::neoplasias pancreáticas, Neoplasm Metastasis, Germ-Line Mutation, Aged, Aged, 80 and over, Gens del càncer, Pàncrees - Tumors, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS], Middle Aged, Female, Pancreatic Neoplasms, Phthalazines, Progression-Free Survival, 3. Good health, FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación::mutación de la línea germinal, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos, enfermedades del sistema digestivo::neoplasias del sistema digestivo::enfermedades del sistema digestivo::neoplasias pancreáticas [ENFERMEDADES], Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS], DISEASES::Digestive System Diseases::Digestive System Neoplasms::Digestive System Diseases::Pancreatic Neoplasms, CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents |
| Description: | Patients with a germline BRCA1 or BRCA2 mutation make up a small subgroup of those with metastatic pancreatic cancer. The poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib has had antitumor activity in this population.We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients who had a germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer and disease that had not progressed during first-line platinum-based chemotherapy. Patients were randomly assigned, in a 3:2 ratio, to receive maintenance olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival, which was assessed by blinded independent central review.Of the 3315 patients who underwent screening, 154 underwent randomization and were assigned to a trial intervention (92 to receive olaparib and 62 to receive placebo). The median progression-free survival was significantly longer in the olaparib group than in the placebo group (7.4 months vs. 3.8 months; hazard ratio for disease progression or death, 0.53; 95% confidence interval [CI], 0.35 to 0.82; P = 0.004). An interim analysis of overall survival, at a data maturity of 46%, showed no difference between the olaparib and placebo groups (median, 18.9 months vs. 18.1 months; hazard ratio for death, 0.91; 95% CI, 0.56 to 1.46; P = 0.68). There was no significant between-group difference in health-related quality of life, as indicated by the overall change from baseline in the global quality-of-life score (on a 100-point scale, with higher scores indicating better quality of life) based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (between-group difference, -2.47 points; 95% CI, -7.27 to 2.33). The incidence of grade 3 or higher adverse events was 40% in the olaparib group and 23% in the placebo group (between-group difference, 16 percentage points; 95% CI, -0.02 to 31); 5% and 2% of the patients, respectively, discontinued the trial intervention because of an adverse event.Among patients with a germline BRCA mutation and metastatic pancreatic cancer, progression-free survival was longer with maintenance olaparib than with placebo. (Funded by AstraZeneca and others; POLO ClinicalTrials.gov number, NCT02184195.). |
| Document Type: | Article |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 1533-4406 0028-4793 |
| DOI: | 10.1056/nejmoa1903387 |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/31157963 http://hdl.handle.net/11351/4637 https://hdl.handle.net/11351/4637 https://discovery.ucl.ac.uk/id/eprint/10076576/ https://pubmed.ncbi.nlm.nih.gov/31157963/ https://snucm.elsevierpure.com/en/publications/maintenance-olaparib-for-germline-brca-mutated-metastatic-pancrea https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810605/figure/F3/ https://moh-it.pure.elsevier.com/en/publications/maintenance-olaparib-for-germline-brca-mutated-metastatic-pancrea https://www.nejm.org/doi/full/10.1056/NEJMoa1903387 https://hdl.handle.net/20.500.11768/124130 https://discovery-pp.ucl.ac.uk/id/eprint/10076576/ |
| Rights: | CC BY NC ND URL: http://www.nejmgroup.org/legal/terms-of-use.htm |
| Accession Number: | edsair.doi.dedup.....b64d853e6f7d1fdbed009f2e8888459d |
| Database: | OpenAIRE |
| ISSN: | 15334406 00284793 |
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| DOI: | 10.1056/nejmoa1903387 |