biostudies-literatureUnknown36(31)Cruz C<h4>Purpose</h4>This multicenter phase II trial evaluated lurbinectedin (PM01183), a selective inhibitor of active transcription of protein-coding genes, in patients with metastatic breast cancer. A unicenter translational substudy assessed potential mechanisms of lurbinectedin resistance.<h4>Patients and methods</h4>Two arms were evaluated according to germline BRCA1/2 status: BRCA1/2 mutated (arm A; n = 54) and unselected ( BRCA1/2 wild-type or unknown status; arm B; n = 35). Lurbinectedin starting dose was a 7-mg flat dose and later, 3.5 mg/m² in arm A. The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST). The translational substudy of resistance mechanisms included exome sequencing (n = 13) and in vivo experiments Journal of clinical oncology : official journal of the American Society of Clinical Oncology3134-3143https://www.ebi.ac.uk/biostudies/studies/S-EPMC6209089biostudies-literatureMulticenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy.PMC6209089Baselga JTelli MLDomchek SMCruz CSoto-Matos ALopez RTung NMFernandez CKahatt CPerez Fidalgo JAVahdat LIsakoff SJAlfaro VGarber JELlop-Guevara AVivancos AArribas JBalmana JGalmarini CMPerez de la Haza AAntolin SArun BKLluch ASerra VfalseMulticenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy.<h4>Purpose</h4>This multicenter phase II trial evaluated lurbinectedin (PM01183), a selective inhibitor of active transcription of protein-coding genes, in patients with metastatic breast cancer. A unicenter translational substudy assessed potential mechanisms of lurbinectedin resistance.<h4>Patients and methods</h4>Two arms were evaluated according to germline BRCA1/2 status: BRCA1/2 mutated (arm A; n = 54) and unselected ( BRCA1/2 wild-type or unknown status; arm B; n = 35). Lurbinectedin starting dose was a 7-mg flat dose and later, 3.5 mg/m² in arm A. The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST). The translational substudy of resistance mechanisms included exome sequencing (n = 13) and in vivo experiments 2018-01-01T00:00:00Z2018 Nov2025-04-04T22:21:14.78Z2019-03-27T00:06:08ZS-EPMC62090893024032710.1200/JCO.2018.78.6558