Randomized, Double-Blind Phase II Trial With Prospective Classification by ATM Protein Level to Evaluate the Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients With Recurrent or Metastatic Gastric Cancer
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Bang, Yung-Jue | - |
dc.contributor.author | Im, Seock-Ah | - |
dc.contributor.author | Lee, Keun-Wook | - |
dc.contributor.author | Cho, Jae Yong | - |
dc.contributor.author | Song, Eun-Kee | - |
dc.contributor.author | Lee, Kyung Hee | - |
dc.contributor.author | Kim, Yeul Hong | - |
dc.contributor.author | Park, Joon Oh | - |
dc.contributor.author | Chun, Hoo Geun | - |
dc.contributor.author | Zang, Dae Young | - |
dc.contributor.author | Fielding, Anitra | - |
dc.contributor.author | Rowbottom, Jacqui | - |
dc.contributor.author | Hodgson, Darren | - |
dc.contributor.author | O'Connor, Mark J. | - |
dc.contributor.author | Yin, Xiaolu | - |
dc.contributor.author | Kim, Woo Ho | - |
dc.date.accessioned | 2021-09-04T10:31:21Z | - |
dc.date.available | 2021-09-04T10:31:21Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2015-11-20 | - |
dc.identifier.issn | 0732-183X | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/91878 | - |
dc.description.abstract | Purpose Gastric cancer cell lines, particularly those with low levels of ataxia telangiectasia mutated (ATM), a key activator of DNA damage response, are sensitive to the poly (ADP-ribose) polymerase inhibitor olaparib. We compared the efficacy of olaparib plus paclitaxel (olaparib/paclitaxel) with paclitaxel alone in patients with recurrent or metastatic gastric cancer and assessed whether low ATM expression is predictive of improved clinical outcome for olaparib/paclitaxel. Patients and Methods In this phase II, double-blind study (Study 39; NCT01063517), patients were randomly assigned to oral olaparib 100 mg twice per day (tablets) plus paclitaxel (80 mg/m(2) per day intravenously on days 1, 8, and 15 of every 28-day cycle) or placebo plus paclitaxel (placebo/paclitaxel), followed by maintenance monotherapy with olaparib (200 mg twice per day) or placebo. The study population was enriched to 50% for patients with low or undetectable ATM levels (ATM(low)). Primary end point was progression-free survival (PFS). Results One hundred twenty-three of 124 randomly assigned patients received treatment (olaparib/paclitaxel, n = 61; placebo/paclitaxel, n = 62). The screening prevalence of ATM(low) patients was 14%. Olaparib/paclitaxel did not lead to a significant improvement in PFS versus placebo/paclitaxel (overall population: hazard ratio [HR], 0.80; median PFS, 3.91 v 3.55 months, respectively; ATM(low) population: HR, 0.74; median PFS, 5.29 v 3.68 months, respectively). However, olaparib/paclitaxel significantly improved overall survival (OS) versus placebo/paclitaxel in both the overall population (HR, 0.56; 80% CI, 0.41 to 0.75; P = .005; median OS, 13.1 v 8.3 months, respectively) and the ATM(low) population (HR, 0.35; 80% CI, 0.22 to 0.56; P = .002; median OS, not reached v 8.2 months, respectively). Olaparib/paclitaxel was generally well tolerated, with no unexpected safety findings. Conclusion Olaparib/paclitaxel is active in the treatment of patients with metastatic gastric cancer, with a greater OS benefit in ATM(low) patients. A phase III trial in this setting is under way. (C) 2015 by American Society of Clinical Oncology | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER SOC CLINICAL ONCOLOGY | - |
dc.subject | PROGRESSION-FREE SURVIVAL | - |
dc.subject | OPEN-LABEL | - |
dc.subject | OVARIAN-CANCER | - |
dc.subject | DNA-DAMAGE | - |
dc.subject | PARP | - |
dc.subject | CELLS | - |
dc.subject | CHEMOTHERAPY | - |
dc.subject | MULTICENTER | - |
dc.subject | DEFICIENCY | - |
dc.subject | EXPRESSION | - |
dc.title | Randomized, Double-Blind Phase II Trial With Prospective Classification by ATM Protein Level to Evaluate the Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients With Recurrent or Metastatic Gastric Cancer | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Yeul Hong | - |
dc.identifier.doi | 10.1200/JCO.2014.60.0320 | - |
dc.identifier.scopusid | 2-s2.0-84947795362 | - |
dc.identifier.wosid | 000366020600007 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CLINICAL ONCOLOGY, v.33, no.33, pp.3858 - + | - |
dc.relation.isPartOf | JOURNAL OF CLINICAL ONCOLOGY | - |
dc.citation.title | JOURNAL OF CLINICAL ONCOLOGY | - |
dc.citation.volume | 33 | - |
dc.citation.number | 33 | - |
dc.citation.startPage | 3858 | - |
dc.citation.endPage | + | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | PROGRESSION-FREE SURVIVAL | - |
dc.subject.keywordPlus | OPEN-LABEL | - |
dc.subject.keywordPlus | OVARIAN-CANCER | - |
dc.subject.keywordPlus | DNA-DAMAGE | - |
dc.subject.keywordPlus | PARP | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | CHEMOTHERAPY | - |
dc.subject.keywordPlus | MULTICENTER | - |
dc.subject.keywordPlus | DEFICIENCY | - |
dc.subject.keywordPlus | EXPRESSION | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.