Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.
Identifieur interne : 001243 ( PubMed/Corpus ); précédent : 001242; suivant : 001244Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.
Auteurs : Elizabeth M. Swisher ; Kevin K. Lin ; Amit M. Oza ; Clare L. Scott ; Heidi Giordano ; James Sun ; Gottfried E. Konecny ; Robert L. Coleman ; Anna V. Tinker ; David M. O'Malley ; Rebecca S. Kristeleit ; Ling Ma ; Katherine M. Bell-Mcguinn ; James D. Brenton ; Janiel M. Cragun ; Ana Oaknin ; Isabelle Ray-Coquard ; Maria I. Harrell ; Elaina Mann ; Scott H. Kaufmann ; Anne Floquet ; Alexandra Leary ; Thomas C. Harding ; Sandra Goble ; Lara Maloney ; Jeff Isaacson ; Andrew R. Allen ; Lindsey Rolfe ; Roman Yelensky ; Mitch Raponi ; Iain A. McneishSource :
- The Lancet. Oncology [ 1474-5488 ] ; 2017.
English descriptors
- KwdEn :
- Aged, Antineoplastic Agents (pharmacology), BRCA1 Protein (genetics), BRCA2 Protein (genetics), Drug Resistance, Neoplasm (drug effects), Fallopian Tube Neoplasms (drug therapy), Fallopian Tube Neoplasms (genetics), Fallopian Tube Neoplasms (pathology), Female, Follow-Up Studies, Germ-Line Mutation (genetics), Humans, Indoles (therapeutic use), International Agencies, Middle Aged, Neoplasm Recurrence, Local (drug therapy), Neoplasm Recurrence, Local (genetics), Neoplasm Recurrence, Local (pathology), Neoplasm Staging, Neoplasms, Glandular and Epithelial (drug therapy), Neoplasms, Glandular and Epithelial (genetics), Neoplasms, Glandular and Epithelial (pathology), Ovarian Neoplasms (drug therapy), Ovarian Neoplasms (genetics), Ovarian Neoplasms (pathology), Peritoneal Neoplasms (drug therapy), Peritoneal Neoplasms (genetics), Peritoneal Neoplasms (pathology), Platinum (pharmacology), Poly(ADP-ribose) Polymerase Inhibitors (therapeutic use), Poly(ADP-ribose) Polymerases (chemistry), Prognosis, Prospective Studies, Salvage Therapy, Survival Rate.
- MESH :
- chemical , chemistry : Poly(ADP-ribose) Polymerases.
- chemical , genetics : BRCA1 Protein, BRCA2 Protein.
- chemical , pharmacology : Antineoplastic Agents, Platinum.
- drug effects : Drug Resistance, Neoplasm.
- drug therapy : Fallopian Tube Neoplasms, Neoplasm Recurrence, Local, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Peritoneal Neoplasms.
- genetics : Fallopian Tube Neoplasms, Germ-Line Mutation, Neoplasm Recurrence, Local, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Peritoneal Neoplasms.
- pathology : Fallopian Tube Neoplasms, Neoplasm Recurrence, Local, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Peritoneal Neoplasms.
- chemical , therapeutic use : Indoles, Poly(ADP-ribose) Polymerase Inhibitors.
- Aged, Female, Follow-Up Studies, Humans, International Agencies, Middle Aged, Neoplasm Staging, Prognosis, Prospective Studies, Salvage Therapy, Survival Rate.
Abstract
Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor.
DOI: 10.1016/S1470-2045(16)30559-9
PubMed: 27908594
Links to Exploration step
pubmed:27908594Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.</title><author><name sortKey="Swisher, Elizabeth M" sort="Swisher, Elizabeth M" uniqKey="Swisher E" first="Elizabeth M" last="Swisher">Elizabeth M. Swisher</name><affiliation><nlm:affiliation>University of Washington, Seattle, WA, USA. Electronic address: swishere@uw.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Lin, Kevin K" sort="Lin, Kevin K" uniqKey="Lin K" first="Kevin K" last="Lin">Kevin K. Lin</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Oza, Amit M" sort="Oza, Amit M" uniqKey="Oza A" first="Amit M" last="Oza">Amit M. Oza</name><affiliation><nlm:affiliation>Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Scott, Clare L" sort="Scott, Clare L" uniqKey="Scott C" first="Clare L" last="Scott">Clare L. Scott</name><affiliation><nlm:affiliation>Royal Melbourne Hospital, Melbourne, VIC, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Giordano, Heidi" sort="Giordano, Heidi" uniqKey="Giordano H" first="Heidi" last="Giordano">Heidi Giordano</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name><affiliation><nlm:affiliation>Foundation Medicine, Cambridge, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Konecny, Gottfried E" sort="Konecny, Gottfried E" uniqKey="Konecny G" first="Gottfried E" last="Konecny">Gottfried E. Konecny</name><affiliation><nlm:affiliation>University of California Los Angeles, Santa Monica, CA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Coleman, Robert L" sort="Coleman, Robert L" uniqKey="Coleman R" first="Robert L" last="Coleman">Robert L. Coleman</name><affiliation><nlm:affiliation>The University of Texas MD Anderson Cancer Center, Houston, TX, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Tinker, Anna V" sort="Tinker, Anna V" uniqKey="Tinker A" first="Anna V" last="Tinker">Anna V. Tinker</name><affiliation><nlm:affiliation>British Columbia Cancer Agency, Vancouver, BC, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="O Malley, David M" sort="O Malley, David M" uniqKey="O Malley D" first="David M" last="O'Malley">David M. O'Malley</name><affiliation><nlm:affiliation>The Ohio State University, James Cancer Center, Columbus, OH, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Kristeleit, Rebecca S" sort="Kristeleit, Rebecca S" uniqKey="Kristeleit R" first="Rebecca S" last="Kristeleit">Rebecca S. Kristeleit</name><affiliation><nlm:affiliation>University College London, Cancer Institute, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Ma, Ling" sort="Ma, Ling" uniqKey="Ma L" first="Ling" last="Ma">Ling Ma</name><affiliation><nlm:affiliation>Rocky Mountain Cancer Centers, Lakewood, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bell Mcguinn, Katherine M" sort="Bell Mcguinn, Katherine M" uniqKey="Bell Mcguinn K" first="Katherine M" last="Bell-Mcguinn">Katherine M. Bell-Mcguinn</name><affiliation><nlm:affiliation>Memorial Sloan-Kettering Cancer Center, New York, NY, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Brenton, James D" sort="Brenton, James D" uniqKey="Brenton J" first="James D" last="Brenton">James D. Brenton</name><affiliation><nlm:affiliation>Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Cragun, Janiel M" sort="Cragun, Janiel M" uniqKey="Cragun J" first="Janiel M" last="Cragun">Janiel M. Cragun</name><affiliation><nlm:affiliation>The University of Arizona Cancer Center, Tucson, AZ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Oaknin, Ana" sort="Oaknin, Ana" uniqKey="Oaknin A" first="Ana" last="Oaknin">Ana Oaknin</name><affiliation><nlm:affiliation>Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Ray Coquard, Isabelle" sort="Ray Coquard, Isabelle" uniqKey="Ray Coquard I" first="Isabelle" last="Ray-Coquard">Isabelle Ray-Coquard</name><affiliation><nlm:affiliation>GINECO, Centre Léon Bérard and University Claude Bernard, Lyon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Harrell, Maria I" sort="Harrell, Maria I" uniqKey="Harrell M" first="Maria I" last="Harrell">Maria I. Harrell</name><affiliation><nlm:affiliation>University of Washington, Seattle, WA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mann, Elaina" sort="Mann, Elaina" uniqKey="Mann E" first="Elaina" last="Mann">Elaina Mann</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Kaufmann, Scott H" sort="Kaufmann, Scott H" uniqKey="Kaufmann S" first="Scott H" last="Kaufmann">Scott H. Kaufmann</name><affiliation><nlm:affiliation>Mayo Clinic, Rochester, MN, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Floquet, Anne" sort="Floquet, Anne" uniqKey="Floquet A" first="Anne" last="Floquet">Anne Floquet</name><affiliation><nlm:affiliation>Institut Bergonié, Bordeaux, France.</nlm:affiliation></affiliation></author><author><name sortKey="Leary, Alexandra" sort="Leary, Alexandra" uniqKey="Leary A" first="Alexandra" last="Leary">Alexandra Leary</name><affiliation><nlm:affiliation>Gustave Roussy Cancer Center and INSERM U981, Villejuif, France.</nlm:affiliation></affiliation></author><author><name sortKey="Harding, Thomas C" sort="Harding, Thomas C" uniqKey="Harding T" first="Thomas C" last="Harding">Thomas C. Harding</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Goble, Sandra" sort="Goble, Sandra" uniqKey="Goble S" first="Sandra" last="Goble">Sandra Goble</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Isaacson, Jeff" sort="Isaacson, Jeff" uniqKey="Isaacson J" first="Jeff" last="Isaacson">Jeff Isaacson</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Allen, Andrew R" sort="Allen, Andrew R" uniqKey="Allen A" first="Andrew R" last="Allen">Andrew R. Allen</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rolfe, Lindsey" sort="Rolfe, Lindsey" uniqKey="Rolfe L" first="Lindsey" last="Rolfe">Lindsey Rolfe</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Yelensky, Roman" sort="Yelensky, Roman" uniqKey="Yelensky R" first="Roman" last="Yelensky">Roman Yelensky</name><affiliation><nlm:affiliation>Foundation Medicine, Cambridge, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mcneish, Iain A" sort="Mcneish, Iain A" uniqKey="Mcneish I" first="Iain A" last="Mcneish">Iain A. Mcneish</name><affiliation><nlm:affiliation>Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:27908594</idno><idno type="pmid">27908594</idno><idno type="doi">10.1016/S1470-2045(16)30559-9</idno><idno type="wicri:Area/PubMed/Corpus">001243</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001243</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.</title><author><name sortKey="Swisher, Elizabeth M" sort="Swisher, Elizabeth M" uniqKey="Swisher E" first="Elizabeth M" last="Swisher">Elizabeth M. Swisher</name><affiliation><nlm:affiliation>University of Washington, Seattle, WA, USA. Electronic address: swishere@uw.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Lin, Kevin K" sort="Lin, Kevin K" uniqKey="Lin K" first="Kevin K" last="Lin">Kevin K. Lin</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Oza, Amit M" sort="Oza, Amit M" uniqKey="Oza A" first="Amit M" last="Oza">Amit M. Oza</name><affiliation><nlm:affiliation>Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Scott, Clare L" sort="Scott, Clare L" uniqKey="Scott C" first="Clare L" last="Scott">Clare L. Scott</name><affiliation><nlm:affiliation>Royal Melbourne Hospital, Melbourne, VIC, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Giordano, Heidi" sort="Giordano, Heidi" uniqKey="Giordano H" first="Heidi" last="Giordano">Heidi Giordano</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Sun, James" sort="Sun, James" uniqKey="Sun J" first="James" last="Sun">James Sun</name><affiliation><nlm:affiliation>Foundation Medicine, Cambridge, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Konecny, Gottfried E" sort="Konecny, Gottfried E" uniqKey="Konecny G" first="Gottfried E" last="Konecny">Gottfried E. Konecny</name><affiliation><nlm:affiliation>University of California Los Angeles, Santa Monica, CA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Coleman, Robert L" sort="Coleman, Robert L" uniqKey="Coleman R" first="Robert L" last="Coleman">Robert L. Coleman</name><affiliation><nlm:affiliation>The University of Texas MD Anderson Cancer Center, Houston, TX, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Tinker, Anna V" sort="Tinker, Anna V" uniqKey="Tinker A" first="Anna V" last="Tinker">Anna V. Tinker</name><affiliation><nlm:affiliation>British Columbia Cancer Agency, Vancouver, BC, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="O Malley, David M" sort="O Malley, David M" uniqKey="O Malley D" first="David M" last="O'Malley">David M. O'Malley</name><affiliation><nlm:affiliation>The Ohio State University, James Cancer Center, Columbus, OH, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Kristeleit, Rebecca S" sort="Kristeleit, Rebecca S" uniqKey="Kristeleit R" first="Rebecca S" last="Kristeleit">Rebecca S. Kristeleit</name><affiliation><nlm:affiliation>University College London, Cancer Institute, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Ma, Ling" sort="Ma, Ling" uniqKey="Ma L" first="Ling" last="Ma">Ling Ma</name><affiliation><nlm:affiliation>Rocky Mountain Cancer Centers, Lakewood, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bell Mcguinn, Katherine M" sort="Bell Mcguinn, Katherine M" uniqKey="Bell Mcguinn K" first="Katherine M" last="Bell-Mcguinn">Katherine M. Bell-Mcguinn</name><affiliation><nlm:affiliation>Memorial Sloan-Kettering Cancer Center, New York, NY, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Brenton, James D" sort="Brenton, James D" uniqKey="Brenton J" first="James D" last="Brenton">James D. Brenton</name><affiliation><nlm:affiliation>Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Cragun, Janiel M" sort="Cragun, Janiel M" uniqKey="Cragun J" first="Janiel M" last="Cragun">Janiel M. Cragun</name><affiliation><nlm:affiliation>The University of Arizona Cancer Center, Tucson, AZ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Oaknin, Ana" sort="Oaknin, Ana" uniqKey="Oaknin A" first="Ana" last="Oaknin">Ana Oaknin</name><affiliation><nlm:affiliation>Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Ray Coquard, Isabelle" sort="Ray Coquard, Isabelle" uniqKey="Ray Coquard I" first="Isabelle" last="Ray-Coquard">Isabelle Ray-Coquard</name><affiliation><nlm:affiliation>GINECO, Centre Léon Bérard and University Claude Bernard, Lyon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Harrell, Maria I" sort="Harrell, Maria I" uniqKey="Harrell M" first="Maria I" last="Harrell">Maria I. Harrell</name><affiliation><nlm:affiliation>University of Washington, Seattle, WA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mann, Elaina" sort="Mann, Elaina" uniqKey="Mann E" first="Elaina" last="Mann">Elaina Mann</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Kaufmann, Scott H" sort="Kaufmann, Scott H" uniqKey="Kaufmann S" first="Scott H" last="Kaufmann">Scott H. Kaufmann</name><affiliation><nlm:affiliation>Mayo Clinic, Rochester, MN, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Floquet, Anne" sort="Floquet, Anne" uniqKey="Floquet A" first="Anne" last="Floquet">Anne Floquet</name><affiliation><nlm:affiliation>Institut Bergonié, Bordeaux, France.</nlm:affiliation></affiliation></author><author><name sortKey="Leary, Alexandra" sort="Leary, Alexandra" uniqKey="Leary A" first="Alexandra" last="Leary">Alexandra Leary</name><affiliation><nlm:affiliation>Gustave Roussy Cancer Center and INSERM U981, Villejuif, France.</nlm:affiliation></affiliation></author><author><name sortKey="Harding, Thomas C" sort="Harding, Thomas C" uniqKey="Harding T" first="Thomas C" last="Harding">Thomas C. Harding</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Goble, Sandra" sort="Goble, Sandra" uniqKey="Goble S" first="Sandra" last="Goble">Sandra Goble</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Maloney, Lara" sort="Maloney, Lara" uniqKey="Maloney L" first="Lara" last="Maloney">Lara Maloney</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Isaacson, Jeff" sort="Isaacson, Jeff" uniqKey="Isaacson J" first="Jeff" last="Isaacson">Jeff Isaacson</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Allen, Andrew R" sort="Allen, Andrew R" uniqKey="Allen A" first="Andrew R" last="Allen">Andrew R. Allen</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rolfe, Lindsey" sort="Rolfe, Lindsey" uniqKey="Rolfe L" first="Lindsey" last="Rolfe">Lindsey Rolfe</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Yelensky, Roman" sort="Yelensky, Roman" uniqKey="Yelensky R" first="Roman" last="Yelensky">Roman Yelensky</name><affiliation><nlm:affiliation>Foundation Medicine, Cambridge, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Raponi, Mitch" sort="Raponi, Mitch" uniqKey="Raponi M" first="Mitch" last="Raponi">Mitch Raponi</name><affiliation><nlm:affiliation>Clovis Oncology, Boulder, CO, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mcneish, Iain A" sort="Mcneish, Iain A" uniqKey="Mcneish I" first="Iain A" last="Mcneish">Iain A. Mcneish</name><affiliation><nlm:affiliation>Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.</nlm:affiliation></affiliation></author></analytic><series><title level="j">The Lancet. Oncology</title><idno type="eISSN">1474-5488</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Antineoplastic Agents (pharmacology)</term><term>BRCA1 Protein (genetics)</term><term>BRCA2 Protein (genetics)</term><term>Drug Resistance, Neoplasm (drug effects)</term><term>Fallopian Tube Neoplasms (drug therapy)</term><term>Fallopian Tube Neoplasms (genetics)</term><term>Fallopian Tube Neoplasms (pathology)</term><term>Female</term><term>Follow-Up Studies</term><term>Germ-Line Mutation (genetics)</term><term>Humans</term><term>Indoles (therapeutic use)</term><term>International Agencies</term><term>Middle Aged</term><term>Neoplasm Recurrence, Local (drug therapy)</term><term>Neoplasm Recurrence, Local (genetics)</term><term>Neoplasm Recurrence, Local (pathology)</term><term>Neoplasm Staging</term><term>Neoplasms, Glandular and Epithelial (drug therapy)</term><term>Neoplasms, Glandular and Epithelial (genetics)</term><term>Neoplasms, Glandular and Epithelial (pathology)</term><term>Ovarian Neoplasms (drug therapy)</term><term>Ovarian Neoplasms (genetics)</term><term>Ovarian Neoplasms (pathology)</term><term>Peritoneal Neoplasms (drug therapy)</term><term>Peritoneal Neoplasms (genetics)</term><term>Peritoneal Neoplasms (pathology)</term><term>Platinum (pharmacology)</term><term>Poly(ADP-ribose) Polymerase Inhibitors (therapeutic use)</term><term>Poly(ADP-ribose) Polymerases (chemistry)</term><term>Prognosis</term><term>Prospective Studies</term><term>Salvage Therapy</term><term>Survival Rate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Poly(ADP-ribose) Polymerases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>BRCA1 Protein</term><term>BRCA2 Protein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents</term><term>Platinum</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Drug Resistance, Neoplasm</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Fallopian Tube Neoplasms</term><term>Neoplasm Recurrence, Local</term><term>Neoplasms, Glandular and Epithelial</term><term>Ovarian Neoplasms</term><term>Peritoneal Neoplasms</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Fallopian Tube Neoplasms</term><term>Germ-Line Mutation</term><term>Neoplasm Recurrence, Local</term><term>Neoplasms, Glandular and Epithelial</term><term>Ovarian Neoplasms</term><term>Peritoneal Neoplasms</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Fallopian Tube Neoplasms</term><term>Neoplasm Recurrence, Local</term><term>Neoplasms, Glandular and Epithelial</term><term>Ovarian Neoplasms</term><term>Peritoneal Neoplasms</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Indoles</term><term>Poly(ADP-ribose) Polymerase Inhibitors</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Female</term><term>Follow-Up Studies</term><term>Humans</term><term>International Agencies</term><term>Middle Aged</term><term>Neoplasm Staging</term><term>Prognosis</term><term>Prospective Studies</term><term>Salvage Therapy</term><term>Survival Rate</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27908594</PMID><DateCreated><Year>2016</Year><Month>12</Month><Day>02</Day></DateCreated><DateCompleted><Year>2017</Year><Month>06</Month><Day>13</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1474-5488</ISSN><JournalIssue CitedMedium="Internet"><Volume>18</Volume><Issue>1</Issue><PubDate><Year>2017</Year><Month>Jan</Month></PubDate></JournalIssue><Title>The Lancet. Oncology</Title><ISOAbbreviation>Lancet Oncol.</ISOAbbreviation></Journal><ArticleTitle>Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.</ArticleTitle><Pagination><MedlinePgn>75-87</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S1470-2045(16)30559-9</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/S1470-2045(16)30559-9</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">ARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA. In ARIEL2 Part 1, patients with recurrent, platinum-sensitive, high-grade ovarian carcinoma were classified into one of three predefined homologous recombination deficiency subgroups on the basis of tumour mutational analysis: BRCA mutant (deleterious germline or somatic), BRCA wild-type and LOH high (LOH high group), or BRCA wild-type and LOH low (LOH low group). We prespecified a cutoff of 14% or more genomic LOH for LOH high. Patients began treatment with oral rucaparib at 600 mg twice per day for continuous 28 day cycles until disease progression or any other reason for discontinuation. The primary endpoint was progression-free survival. All patients treated with at least one dose of rucaparib were included in the safety analyses and all treated patients who were classified were included in the primary endpoint analysis. This trial is registered with ClinicalTrials.gov, number NCT01891344. Enrolment into ARIEL2 Part 1 is complete, although an extension (Part 2) is ongoing.</AbstractText><AbstractText Label="FINDINGS" NlmCategory="RESULTS">256 patients were screened and 206 were enrolled between Oct 30, 2013, and Dec 19, 2014. At the data cutoff date (Jan 18, 2016), 204 patients had received rucaparib, with 28 patients remaining in the study. 192 patients could be classified into one of the three predefined homologous recombination deficiency subgroups: BRCA mutant (n=40), LOH high (n=82), or LOH low (n=70). Tumours from 12 patients were established as BRCA wild-type, but could not be classified for LOH, because of insufficient neoplastic nuclei in the sample. The median duration of treatment for the 204 patients was 5·7 months (IQR 2·8-10·1). 24 patients in the BRCA mutant subgroup, 56 patients in the LOH high subgroup, and 59 patients in the LOH low subgroup had disease progression or died. Median progression-free survival after rucaparib treatment was 12·8 months (95% CI 9·0-14·7) in the BRCA mutant subgroup, 5·7 months (5·3-7·6) in the LOH high subgroup, and 5·2 months (3·6-5·5) in the LOH low subgroup. Progression-free survival was significantly longer in the BRCA mutant (hazard ratio 0·27, 95% CI 0·16-0·44, p<0·0001) and LOH high (0·62, 0·42-0·90, p=0·011) subgroups compared with the LOH low subgroup. The most common grade 3 or worse treatment-emergent adverse events were anaemia or decreased haemoglobin (45 [22%] patients), and elevations in alanine aminotransferase or aspartate aminotransferase (25 [12%]). Common serious adverse events included small intestinal obstruction (10 [5%] of 204 patients), malignant neoplasm progression (10 [5%]), and anaemia (nine [4%]). Three patients died during the study (two because of disease progression and one because of sepsis and disease progression). No treatment-related deaths occurred.</AbstractText><AbstractText Label="INTERPRETATION" NlmCategory="CONCLUSIONS">In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas. Our results suggest that assessment of tumour LOH can be used to identify patients with BRCA wild-type platinum-sensitive ovarian cancers who might benefit from rucaparib. These results extend the potential usefulness of PARP inhibitors in the treatment setting beyond BRCA mutant tumours.</AbstractText><AbstractText Label="FUNDING" NlmCategory="BACKGROUND">Clovis Oncology, US Department of Defense Ovarian Cancer Research Program, Stand Up To Cancer-Ovarian Cancer Research Fund Alliance-National Ovarian Cancer Coalition Dream Team Translational Research Grant, and V Foundation Translational Award.</AbstractText><CopyrightInformation>Copyright © 2017 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Swisher</LastName><ForeName>Elizabeth M</ForeName><Initials>EM</Initials><AffiliationInfo><Affiliation>University of Washington, Seattle, WA, USA. Electronic address: swishere@uw.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Kevin K</ForeName><Initials>KK</Initials><AffiliationInfo><Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oza</LastName><ForeName>Amit M</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scott</LastName><ForeName>Clare L</ForeName><Initials>CL</Initials><AffiliationInfo><Affiliation>Royal Melbourne Hospital, Melbourne, VIC, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Giordano</LastName><ForeName>Heidi</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>James</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Foundation Medicine, Cambridge, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Konecny</LastName><ForeName>Gottfried E</ForeName><Initials>GE</Initials><AffiliationInfo><Affiliation>University of California Los Angeles, Santa Monica, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coleman</LastName><ForeName>Robert L</ForeName><Initials>RL</Initials><AffiliationInfo><Affiliation>The University of Texas MD Anderson Cancer Center, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tinker</LastName><ForeName>Anna V</ForeName><Initials>AV</Initials><AffiliationInfo><Affiliation>British Columbia Cancer Agency, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>O'Malley</LastName><ForeName>David M</ForeName><Initials>DM</Initials><AffiliationInfo><Affiliation>The Ohio State University, James Cancer Center, Columbus, OH, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kristeleit</LastName><ForeName>Rebecca S</ForeName><Initials>RS</Initials><AffiliationInfo><Affiliation>University College London, Cancer Institute, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ma</LastName><ForeName>Ling</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Rocky Mountain Cancer Centers, Lakewood, CO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bell-McGuinn</LastName><ForeName>Katherine M</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>Memorial Sloan-Kettering Cancer Center, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brenton</LastName><ForeName>James D</ForeName><Initials>JD</Initials><AffiliationInfo><Affiliation>Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cragun</LastName><ForeName>Janiel M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>The University of Arizona Cancer Center, Tucson, AZ, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oaknin</LastName><ForeName>Ana</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ray-Coquard</LastName><ForeName>Isabelle</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>GINECO, Centre Léon Bérard and University Claude Bernard, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Harrell</LastName><ForeName>Maria I</ForeName><Initials>MI</Initials><AffiliationInfo><Affiliation>University of Washington, Seattle, WA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mann</LastName><ForeName>Elaina</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kaufmann</LastName><ForeName>Scott H</ForeName><Initials>SH</Initials><AffiliationInfo><Affiliation>Mayo Clinic, Rochester, MN, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Floquet</LastName><ForeName>Anne</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Institut Bergonié, Bordeaux, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Leary</LastName><ForeName>Alexandra</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Gustave Roussy Cancer Center and INSERM U981, Villejuif, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Harding</LastName><ForeName>Thomas C</ForeName><Initials>TC</Initials><AffiliationInfo><Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goble</LastName><ForeName>Sandra</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maloney</LastName><ForeName>Lara</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Isaacson</LastName><ForeName>Jeff</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Allen</LastName><ForeName>Andrew R</ForeName><Initials>AR</Initials><AffiliationInfo><Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rolfe</LastName><ForeName>Lindsey</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yelensky</LastName><ForeName>Roman</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Foundation Medicine, Cambridge, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Raponi</LastName><ForeName>Mitch</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Clovis Oncology, Boulder, CO, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McNeish</LastName><ForeName>Iain A</ForeName><Initials>IA</Initials><AffiliationInfo><Affiliation>Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>ClinicalTrials.gov</DataBankName><AccessionNumberList><AccessionNumber>NCT01891344</AccessionNumber></AccessionNumberList></DataBank></DataBankList><GrantList CompleteYN="Y"><Grant><GrantID>G0501974</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D017427">Clinical Trial, Phase II</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016448">Multicenter Study</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>11</Month><Day>29</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Lancet Oncol</MedlineTA><NlmUniqueID>100957246</NlmUniqueID><ISSNLinking>1470-2045</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000970">Antineoplastic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019313">BRCA1 Protein</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C492913">BRCA1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D024682">BRCA2 Protein</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C551750">BRCA2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007211">Indoles</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000067856">Poly(ADP-ribose) Polymerase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>49DFR088MY</RegistryNumber><NameOfSubstance UI="D010984">Platinum</NameOfSubstance></Chemical><Chemical><RegistryNumber>8237F3U7EH</RegistryNumber><NameOfSubstance UI="C531549">rucaparib</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.4.2.30</RegistryNumber><NameOfSubstance UI="D011065">Poly(ADP-ribose) Polymerases</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Disease" UI="C538090">Ovarian epithelial cancer</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000970" MajorTopicYN="N">Antineoplastic Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019313" MajorTopicYN="N">BRCA1 Protein</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D024682" MajorTopicYN="N">BRCA2 Protein</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019008" MajorTopicYN="N">Drug Resistance, Neoplasm</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005185" MajorTopicYN="N">Fallopian Tube Neoplasms</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005500" MajorTopicYN="N">Follow-Up Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018095" MajorTopicYN="N">Germ-Line Mutation</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" 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