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dc.contributor.authorRee, Anne Hansen
dc.contributor.authorNygaard, Vigdis
dc.contributor.authorPedersen, Kjetil Boye
dc.contributor.authorHeinrich, Daniel
dc.contributor.authorDueland, Svein
dc.contributor.authorBergheim, Inger Riise
dc.contributor.authorJohansen, Christin
dc.contributor.authorBeiske, Klaus
dc.contributor.authorNegård, Anne
dc.contributor.authorLund-Iversen, Marius
dc.contributor.authorNygaard, Vegard
dc.contributor.authorHovig, Eivind
dc.contributor.authorNakken, Sigve
dc.contributor.authorNasser, Salah
dc.contributor.authorJulsrud, Lars
dc.contributor.authorReisse, Claudius
dc.contributor.authorRuud, Espen Asak
dc.contributor.authorKristensen, Vessela N.
dc.contributor.authorFlørenes, Vivi Ann
dc.contributor.authorGeitvik, Gry
dc.contributor.authorLingjærde, Ole Christian
dc.contributor.authorBørresen-Dale, Anne-Lise
dc.contributor.authorRussnes, Hege Elisabeth Giercksky
dc.contributor.authorMælandsmo, Gunhild Mari
dc.contributor.authorFlatmark, Kjersti
dc.date.accessioned2020-06-30T07:02:12Z
dc.date.available2020-06-30T07:02:12Z
dc.date.issued2020-03-25
dc.description.abstract<i>Background</i>: In precision cancer medicine, the challenge is to prioritize DNA driver events, account for resistance markers, and procure sufficient information for treatment that maintains patient safety. The MetAction project, exploring how tumor molecular vulnerabilities predict therapy response, first established the required workflow for DNA sequencing and data interpretation (2014–2015). Here, we employed it to identify molecularly matched therapy and recorded outcome in end-stage cancer (2016–2019).<p><p> <i>Material and methods</i>: Metastatic tissue from 26 patients (16 colorectal cancer cases) was sequenced by the Oncomine assay. The study tumor boards interpreted called variants with respect to sensitivity or resistance to matched therapy and recommended single-agent or combination treatment if considered tolerable. The primary endpoint was the rate of progression-free survival 1.3-fold longer than for the most recent systemic therapy. The objective response rate and overall survival were secondary endpoints.<p><p> <i>Results</i>: Both common and rare actionable alterations were identified. Thirteen patients were found eligible for therapy following review of tumor sensitivity and resistance variants and patient tolerability. The interventions were inhibitors of ALK/ROS1-, BRAF-, EGFR-, FGFR-, mTOR-, PARP-, or PD-1-mediated signaling for 2–3 cases each. Among 10 patients who received treatment until radiologic evaluation, 6 (46% of the eligible cases) met the primary endpoint. Four colorectal cancer patients (15% of the total study cohort) had objective response. The only serious adverse event was a transient colitis, which appeared in 1 of the 2 patients given PD-1 inhibitor with complete response. Apart from those two, overall survival was similar for patients who did and did not receive study treatment.<p><p> <i>Conclusions</i>: The systematic MetAction approach may point forward to a refined framework for how to interpret the complexity of sensitivity <i>versus</i> resistance and patient safety that resides in tumor sequence data, for the possibly improved outcome of precision cancer medicine in future studies.en_US
dc.identifier.citationRee AH, Nygaard V, Pedersen KB, Heinrich D, Dueland S, Bergheim IR, Johansen C, Beiske K, Negård A, Lund-Iversen M, Nygaard V, Hovig E, Nakken S, Nasser S, Julsrud L, Reisse C, Ruud EA, Kristensen VN, Flørenes VA, Geitvik G, Lingjærde OC, Børresen-Dale A, Russnes HE, Mælandsmo GM, Flatmark K. Molecularly matched therapy in the context of sensitivity, resistance, and safety; patient outcomes in end-stage cancer - the MetAction study. Acta Oncologica. 2020:1-10en_US
dc.identifier.cristinIDFRIDAID 1813310
dc.identifier.doi10.1080/0284186X.2020.1742377
dc.identifier.issn0284-186X
dc.identifier.issn1651-226X
dc.identifier.urihttps://hdl.handle.net/10037/18698
dc.language.isoengen_US
dc.publisherTaylor & Francisen_US
dc.relation.journalActa Oncologica
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/BEHANDLING/218325/Norway/MetAction: Actionable Targets in Cancer Metastasis - from Bed to Bench to Byte to Bedside/MetAction/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700en_US
dc.subjectVDP::Medisinske Fag: 700en_US
dc.titleMolecularly matched therapy in the context of sensitivity, resistance, and safety; patient outcomes in end-stage cancer - the MetAction studyen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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