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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

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dc.contributor.authorBang, Yung-Jue-
dc.contributor.authorIm, Seock-Ah-
dc.contributor.authorLee, Keun-Wook-
dc.contributor.authorCho, Jae Yong-
dc.contributor.authorSong, Eun-Kee-
dc.contributor.authorLee, Kyung Hee-
dc.contributor.authorKim, Yeul Hong-
dc.contributor.authorPark, Joon Oh-
dc.contributor.authorChun, Hoo Geun-
dc.contributor.authorZang, Dae Young-
dc.contributor.authorFielding, Anitra-
dc.contributor.authorRowbottom, Jacqui-
dc.contributor.authorHodgson, Darren-
dc.contributor.authorO'Connor, Mark J.-
dc.contributor.authorYin, Xiaolu-
dc.contributor.authorKim, Woo Ho-
dc.date.accessioned2021-01-31T12:01:36Z-
dc.date.available2021-01-31T12:01:36Z-
dc.date.issued2015-11-
dc.identifier.citationJournal of Clinical Oncology, Vol.33 No.33, pp.3858-3865-
dc.identifier.issn0732-183X-
dc.identifier.other59799-
dc.identifier.urihttps://hdl.handle.net/10371/173217-
dc.description.abstractPurpose 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.titleRandomized, 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.typeArticle-
dc.contributor.AlternativeAuthor방영주-
dc.identifier.doi10.1200/JCO.2014.60.0320-
dc.citation.journaltitleJournal of Clinical Oncology-
dc.identifier.scopusid2-s2.0-84947795362-
dc.citation.endpage3865-
dc.citation.number33-
dc.citation.startpage3858-
dc.citation.volume33-
dc.identifier.urlhttp://ascopubs.org/doi/10.1200/JCO.2014.60.0320-
dc.identifier.rimsid59799-
dc.identifier.sci000366020600007-
dc.contributor.affiliatedAuthorBang, Yung-Jue-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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