PMID- 29623421 OWN - NLM STAT- MEDLINE DCOM- 20180612 LR - 20181202 IS - 1432-1335 (Electronic) IS - 0171-5216 (Print) IS - 0171-5216 (Linking) VI - 144 IP - 6 DP - 2018 Jun TI - Trabectedin plus pegylated liposomal doxorubicin (PLD) for patients with platinum-sensitive recurrent ovarian cancer: a prospective, observational, multicenter study. PG - 1185-1195 LID - 10.1007/s00432-018-2637-1 [doi] AB - PURPOSE: The OVA-YOND study is the first prospective, non-interventional trial designed to evaluate trabectedin (1.1 mg/m(2)) plus PLD (30 mg/m(2)) in patients with platinum-sensitive recurrent ovarian cancer (ROC), given according to the marketing authorization in real-life clinical practice across Germany. METHODS: Eligible patients were adults with platinum-sensitive ROC, pretreated with >/= 1 platinum-containing regimen/s. The primary endpoint was to assess safety/tolerability of the combination. RESULTS: Seventy-seven patients with platinum-sensitive relapse from 31 sites were evaluated. Patients received a median of 6 cycles (range 1-21) with 39 patients (50.6%) receiving >/= 6 cycles. Median treatment duration was 4.2 months (range 0.7-18.8), mostly on an outpatient basis (88.3% of patients). Most common grade 3/4 trabectedin-related adverse events (AEs) were leukopenia (18.2%), neutropenia (15.6%), thrombocytopenia (9.1%), alanine (7.8%) and aspartate aminotransferase (6.5%) increase, and nausea/vomiting (5.2% each). Neutropenia (18.2%), leukopenia (15.6%), thrombocytopenia (10.4%), and nausea/vomiting (5.2% each) were the most frequent grade 3/4 PLD-related AEs. No deaths attributed to drug-related AEs or unexpected AEs occurred. Five patients (6.5%) had a complete response and 19 patients (24.7%) achieved a partial response for an objective response rate of 31.2% with median response duration of 6.25 months. Sixteen patients (20.8%) had disease stabilization for a disease control rate of 51.9%. Median progression-free survival was 6.3 months and median overall survival was 16.4 months. CONCLUSION: Trabectedin plus PLD confer clinically meaningful benefit to pre-treated patients with platinum-sensitive ROC, being comparable to those previously observed in selected populations from clinical trials and with a manageable safety profile. FAU - Runnebaum, Ingo B AU - Runnebaum IB AD - Department of Gynecology and Reproductive Medicine and ESGO Training Center for Gynecologic Oncology, Jena University Hospital, University Women's Hospital, Am Klinikum 1, 07747, Jena, Germany. ingo.runnebaum@med.uni-jena.de. FAU - Reichert, Dietmar AU - Reichert D AD - Medizinische Studiengesellschaft NORD-WEST GmbH, Medical oncology, Kuhlenstrasse 53d, 26655, Westerstede, Germany. FAU - Ringsdorf, Uta AU - Ringsdorf U AD - Lahn-Dill-Kliniken GmbH, Gynecology and Obstetrics, Forsthausstrasse 1, 35578, Wetzlar, Germany. FAU - Kuther, Markus AU - Kuther M AD - Municipal Hospital Kiel, Medical oncology, Chemnitzstrasse 33, 24116, Kiel, Germany. FAU - Hesse, Tobias AU - Hesse T AD - Department of Gynecology and Obstetrics, Agaplesion Diakonieklinikum Rotenburg GmbH, Elise-Averdieck-Strasse 17, 27356, Rotenburg (Wumme), Germany. FAU - Sehouli, Jalid AU - Sehouli J AD - Department of Gynecology with Center for Oncological Surgery, Campus Virchow Klinikum, Benjamin Franklin Charite Comprehensive Cancer Center and European Competence Center for Ovarian Cancer, Medical University of Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. FAU - Wimberger, Pauline AU - Wimberger P AD - Medical Faculty and University Hospital Carl Gustav Carus, Gynecology and Obstetrics, TU Dresden, Fetscherstr. 74, 01397, Dresden, Germany. LA - eng GR - ET-D-022-11/PharmaMar/ PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20180406 PL - Germany TA - J Cancer Res Clin Oncol JT - Journal of cancer research and clinical oncology JID - 7902060 RN - 0 (Dioxoles) RN - 0 (Organoplatinum Compounds) RN - 0 (Tetrahydroisoquinolines) RN - 0 (liposomal doxorubicin) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 80168379AG (Doxorubicin) RN - ID0YZQ2TCP (Trabectedin) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Dioxoles/administration & dosage/adverse effects MH - Disease-Free Survival MH - Doxorubicin/administration & dosage/adverse effects/analogs & derivatives MH - Female MH - Humans MH - Middle Aged MH - Neoplasm Recurrence, Local/*drug therapy MH - Organoplatinum Compounds/pharmacology MH - Ovarian Neoplasms/*drug therapy MH - Polyethylene Glycols/administration & dosage/adverse effects MH - Prospective Studies MH - Tetrahydroisoquinolines/administration & dosage/adverse effects MH - Trabectedin PMC - PMC5948298 OTO - NOTNLM OT - Observational trial OT - Pegylated liposomal doxorubicin (PLD) OT - Trabectedin COIS- CONFLICT OF INTEREST: Ingo Runnebaum has received funding for this study and a speaker honorarium from PharmaMar and was a member of advisory board of PharmaMar. Jalid Sehouli is a member of advisory board of Roche, Clovis, Tesaro and Astra Zeneca, and has received founding from PharmaMar and Medac. Pauline Wimberger has received a speaker honorarium from PharmaMar for scientific talks. All other authors declare they have no conflict of interest. ETHICAL APPROVAL: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards, guidelines for Good Pharmacoepidemiology Practice and the German Drug Law (AMG, section sign 67[6]), and were approved by the institutional review boards of each participating center. INFORMED CONSENT: Informed consent was obtained from all individual participants included in the study. EDAT- 2018/04/07 06:00 MHDA- 2018/06/13 06:00 PMCR- 2018/04/06 CRDT- 2018/04/07 06:00 PHST- 2018/03/21 00:00 [received] PHST- 2018/03/28 00:00 [accepted] PHST- 2018/04/07 06:00 [pubmed] PHST- 2018/06/13 06:00 [medline] PHST- 2018/04/07 06:00 [entrez] PHST- 2018/04/06 00:00 [pmc-release] AID - 10.1007/s00432-018-2637-1 [pii] AID - 2637 [pii] AID - 10.1007/s00432-018-2637-1 [doi] PST - ppublish SO - J Cancer Res Clin Oncol. 2018 Jun;144(6):1185-1195. doi: 10.1007/s00432-018-2637-1. Epub 2018 Apr 6.