PMID- 34521554 OWN - NLM STAT- MEDLINE DCOM- 20220106 LR - 20220106 IS - 1095-6859 (Electronic) IS - 0090-8258 (Linking) VI - 163 IP - 2 DP - 2021 Nov TI - Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL). PG - 237-245 LID - S0090-8258(21)01330-5 [pii] LID - 10.1016/j.ygyno.2021.08.032 [doi] AB - OBJECTIVE: The randomized phase 3 CORAIL trial evaluated whether lurbinectedin improved progression-free survival (PFS) compared to pegylated liposomal doxorubicin (PLD) or topotecan in patients with platinum-resistant ovarian cancer. METHODS: Patients were randomly assigned (1:1) to lurbinectedin 3.2 mg/m(2) 1-h i.v. infusion q3wk (experimental arm), versus PLD 50 mg/m(2) 1-h i.v. infusion q4wk or topotecan 1.50 mg/m(2) 30-min i.v. infusion Days 1-5 q3wk (control arm). Stratification factors were PS (0 vs. >/=1), prior PFI (1-3 months vs. >3 months), and prior chemotherapy lines (1-2 vs. 3). The primary endpoint was PFS by Independent Review Committee in all randomized patients. This study was registered with ClinicalTrials.gov, NCT02421588. RESULTS: 442 patients were randomized: 221 in lurbinectedin arm and 221 in control arm (127 PLD and 94 topotecan). With a median follow-up of 25.6 months, median PFS was 3.5 months (95% CI, 2.1-3.7) in the lurbinectedin arm and 3.6 months (95% CI, 2.7-3.8) in the control arm (stratified log-rank p = 0.6294; HR = 1.057). Grade >/= 3 treatment-related adverse events (AEs) were most frequent in the control arm: 64.8% vs. 47.9% (p = 0.0005), mainly due to hematological toxicities. The most common grade >/= 3 AEs were: fatigue (7.3% of patients) and nausea (5.9%) with lurbinectedin; mucosal inflammation (8.5%) and fatigue (8.0%) in the control arm. CONCLUSIONS: The primary endpoint of improvement in PFS was not met. Lurbinectedin showed similar antitumor efficacy and was better tolerated than current standard of care in patients with platinum-resistant ovarian cancer. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Gaillard, Stephanie AU - Gaillard S AD - Duke Cancer Institute, Durham, USA. Electronic address: stephanie.gaillard@jhmi.edu. FAU - Oaknin, Ana AU - Oaknin A AD - Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. FAU - Ray-Coquard, Isabelle AU - Ray-Coquard I AD - GINECO, Centre Leon Berard and University Claude Bernard, Lyon, France. FAU - Vergote, Ignace AU - Vergote I AD - University Hospital Leuven, Leuven, Belgium. FAU - Scambia, Giovanni AU - Scambia G AD - Fondazione Policlinico Universitario A Gemelli IRCCS, Roma, Italy. FAU - Colombo, Nicoletta AU - Colombo N AD - University of Milan-Bicocca and European Institute of Oncology, IRCCS, Milan, Italy. FAU - Fernandez, Cristian AU - Fernandez C AD - Pharma Mar S.A., Clinical R&D, Colmenar Viejo, Madrid, Spain. FAU - Alfaro, Vicente AU - Alfaro V AD - Pharma Mar S.A., Clinical R&D, Colmenar Viejo, Madrid, Spain. FAU - Kahatt, Carmen AU - Kahatt C AD - Pharma Mar S.A., Clinical R&D, Colmenar Viejo, Madrid, Spain. FAU - Nieto, Antonio AU - Nieto A AD - Pharma Mar S.A., Clinical R&D, Colmenar Viejo, Madrid, Spain. FAU - Zeaiter, Ali AU - Zeaiter A AD - Pharma Mar S.A., Clinical R&D, Colmenar Viejo, Madrid, Spain. FAU - Aracil, Miguel AU - Aracil M AD - Pharma Mar S.A., Clinical R&D, Colmenar Viejo, Madrid, Spain. FAU - Vidal, Laura AU - Vidal L AD - Syneos Health, Barcelona, Spain. FAU - Pardo-Burdalo, Beatriz AU - Pardo-Burdalo B AD - Institut Catala Oncologia, Hospital Duran i Reynals, Barcelona, Spain. FAU - Papai, Zsuzsanna AU - Papai Z AD - Magyar Honvedseg Egeszsegugyi Kozpont, Budapest, Hungary. FAU - Kristeleit, Rebecca AU - Kristeleit R AD - University College of London Hospital; London, United Kingdom. FAU - O'Malley, David M AU - O'Malley DM AD - James Comprehensive Cancer Center - Wexner Medical Center, The Ohio State University, Columbus, USA. FAU - Benjamin, Ivor AU - Benjamin I AD - Arizona Center for Cancer Care, Glendale, USA. FAU - Pautier, Patricia AU - Pautier P AD - Institut Gustave-Roussy, Villejuif, France. FAU - Lorusso, Domenica AU - Lorusso D AD - Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano, and Fondazione Policlinico Gemelli IRCCS, Rome, Italy. LA - eng SI - ClinicalTrials.gov/NCT02421588 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210911 PL - United States TA - Gynecol Oncol JT - Gynecologic oncology JID - 0365304 RN - 0 (Carbolines) RN - 0 (Heterocyclic Compounds, 4 or More Rings) RN - 0 (PM 01183) RN - 0 (liposomal doxorubicin) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 7M7YKX2N15 (Topotecan) RN - 80168379AG (Doxorubicin) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carbolines/*administration & dosage/adverse effects MH - Doxorubicin/administration & dosage/adverse effects/*analogs & derivatives MH - Drug Resistance, Neoplasm MH - Female MH - Heterocyclic Compounds, 4 or More Rings/*administration & dosage/adverse effects MH - Humans MH - Infusions, Intravenous MH - Middle Aged MH - Ovarian Neoplasms/*drug therapy/mortality/pathology MH - Polyethylene Glycols/administration & dosage/adverse effects MH - Progression-Free Survival MH - Topotecan/*administration & dosage/adverse effects OTO - NOTNLM OT - Lurbinectedin OT - Ovarian cancer OT - Phase III study OT - Platinum-resistant COIS- Declaration of Competing Interest Stephanie Gaillard reports grants and personal fees from PharmaMar, during the conduct of the study; and grants and personal fees from AstraZeneca; grants from Abbvie, Pfizer, Rigel, Iovance, Tesaro, Genentech/Roche; and personal fees from Immunogen and Sermonix, outside the submitted work. In addition, Dr. Gaillard has a patent PCT/US2019/026669 licensed to Sermonix. Ana Oaknin reports personal fees for support for travel and or accommodation from Roche, AstraZeneca, PharmaMar, and Clovis Oncology; personal fees from Tesaro, Immunogen, and Genmab; and site grants from Abbie Deutchland, Ability Pharmaceuticals Advaxis Inc., Aeterna Zentaris, Amgen SA, Aprea Therapeutics AB, Clovis Oncology Inc., Eisai Ltd., F. Hoffmann-La Roche Ltd., Regeneron Pharmaceuticals, Immunogen Inc., Merck Sharp & Dohme de Espana SA, Millennium Pharmaceutials Inc., PharmaMar, Tesaro Inc., Bristol Meyers Squibb, and BMS, outside the submitted work. Isabelle Ray-Coquard reports personal fees from Roche, Astra Zeneca, and Clovis; grants and personal fees from GSK and MSD, and personal fees from Amgen, Advaxis, PharmaMar, Genmab, and Mersana, outside the submitted work. Ignace Vergote reports fees for consulting paid to his university from MSD Belgium, Roche NV, Genmab A/S-Genmab B.V.-Genmab US, F. Hoffman-La Roche Ltd., Pharmamar-Doctaforum Servicios SL, Millennium Pharmaceuticals, Clovis Oncology, Astrazeneca NV + AstraZeneca UK Ltd. + AstraZeneca Belux, Tesaro Inc. + Tesaro Bio GmbH, Oncoinvent AS, Immunogen Inc., Sotio a.s., Amgen Europe, Carrick Therapeutics, Debiopharm International SA, GSK GlaxoSmithKline Pharmaceuticals, Medical University of Vienna, Octimet Oncology NV, Deciphera Pharmaceuticals, and Verastem Oncology; grants from Amgen and Roche; and contracted research from Oncoinvent AS and Genmab, outside the submitted work, and accommodations/travel expenses from Amgen, MSD/Merck, Roche, Astrazeneca and Tesaro. Nicoletta Colombo reports personal fees from Roche, PharmaMar, Astra Zeneca, MSD, Tesaro, GSK, Clovis, Amgen, Pfizer, Biogen and BIOCAD, outside the submitted work. Cristian Fernandez, Vicente Alfaro, Carmen Kahatt, Antonio Nieto, Ali Zeatier, and Miguel Aracil report grants from the Centro para el Desarrollo Tecnologico Industrial (CDTI) during the conduct of the study; and personal fees for salary as full time employee and stock ownership from Pharma Mar, outside the submitted work. Rebecca Kristeleit reports grants, personal fees and non-financial support from Clovis Oncology and Basilea; grants and personal fees from MSD; personal fees and non-financial support from AstraZeneca and GSK/Tesaro; and personal fees from Merck, Roche and Sotio, outside the submitted work. David M. O'Malley reports non-financial support and other from Pharma Mar during the conduct of the study (the Institution received funding for the trial, and manuscript preparation was provided); and personal fees or other for consulting/advisory board/steering committee, institutional support for clinical trial from AstraZeneca, Clovis, Tesaro, Immunogen, Ambry, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc., Cerulean Pharma, GOG Foundation, Bristol-Myers Squibb Co, Serono Inc., TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc., inVentiv Health Clinical, Iovance Biotherapeutics, Inc., PRA Intl, Myriad Genetics, Eisai, Agenus, GSK, Tarveda, Merck, and GenMab, outside the submitted work. Domenica Lorusso reports personal fees for advisory board, principal investigator for registration trials, travel support and hospital meeting from Roche, Tesaro/GSK, Clovis, Merck, PharmaMar, Immunogen, Genmab, Amgen, and Astra Zeneca; institutional grant for research from Tesaro/GSK, Clovis, and PharmaMar, outside the submitted work. All remaining authors have declared no conflicts of interest. EDAT- 2021/09/16 06:00 MHDA- 2022/01/07 06:00 CRDT- 2021/09/15 05:53 PHST- 2021/04/19 00:00 [received] PHST- 2021/08/20 00:00 [revised] PHST- 2021/08/30 00:00 [accepted] PHST- 2021/09/16 06:00 [pubmed] PHST- 2022/01/07 06:00 [medline] PHST- 2021/09/15 05:53 [entrez] AID - S0090-8258(21)01330-5 [pii] AID - 10.1016/j.ygyno.2021.08.032 [doi] PST - ppublish SO - Gynecol Oncol. 2021 Nov;163(2):237-245. doi: 10.1016/j.ygyno.2021.08.032. Epub 2021 Sep 11.