{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T01:25:09Z","timestamp":1789867509684,"version":"4.0.1"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VALG_CT_SPERIM_22_01"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Objective: While PLD-Trabectedin is an approved treatment for relapsed platinum-sensitive ovarian cancer, its efficacy and tolerability has so far not been tested extensively in patients who progress after poly ADP-ribose polymerase inhibitor (PARPi) treatment. Methodology: This multicenter, retrospective analysis had the objective of comparing patients receiving PLD-Trabectedin after being treated with PARP-I (cases) with PARPi-na\u00efve patients. Descriptive and survival analyses were performed for each group. Results: Data from 166 patients were collected, composed of 109 cases and 57 controls. In total, 135 patients were included in our analyses, composing 46 controls and 89 cases. The median PFS was 11 months (95% IC 10\u201312) in the control group vs. 8 months (95% IC 6\u20139) in the case group (p value 0.0017). The clinical benefit rate was evaluated, with an HR for progression of 2.55 (1.28\u20135.06) for the case group (p value 0.008), persisting when adjusted for BRCA and line with treatment. We compared hematological toxicity, gastro-intestinal toxicity, hand\u2013foot syndrome (HFS), fatigue, and liver toxicity, and no statistically significant disparity was noted, except for HFS with a p value of 0.006. The distribution of G3 and G4 toxicities was also equally represented. Conclusion: The MITO39 study showed a statistically significant difference in terms of PFS, suggesting that previous exposure to PARPi might inhibit the efficacy of PLD-Trabectedin. Regarding tolerability, no remarkable disparity was noted; PLD-Trabectedin was confirmed to be a well-tolerated scheme in both groups. To our knowledge, these are the first data regarding this topic, which we deem to be of great relevance in the current landscape.<\/jats:p>","DOI":"10.3390\/cancers16010041","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T11:24:33Z","timestamp":1703071473000},"page":"41","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["MITO39: Efficacy and Tolerability of Pegylated Liposomal Doxorubicin (PLD)\u2013Trabectedin in the Treatment of Relapsed Ovarian Cancer after Maintenance Therapy with PARP Inhibitors\u2014A Multicenter Italian Trial in Ovarian Cancer Observational Case-Control Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Margherita","family":"Turinetto","sequence":"first","affiliation":[{"name":"Department of Oncology, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ricotti","sequence":"additional","affiliation":[{"name":"Clinical Trial, Ordine Mauriziano Hospital, 10128 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Pisano","sequence":"additional","affiliation":[{"name":"Department of Urology and Gynecology, National Cancer Institute IRCCS Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Zamagni","sequence":"additional","affiliation":[{"name":"Addarii Medical Oncology, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8055-5086","authenticated-orcid":false,"given":"Chiara","family":"Cassani","sequence":"additional","affiliation":[{"name":"Unit of Obstetrics and Gynecology, IRCCS Matteo Foundation, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Malaguti","sequence":"additional","affiliation":[{"name":"Medical Oncology 1, Regina Elena National Cancer Institute\u2013IRCCS, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Baldoni","sequence":"additional","affiliation":[{"name":"Oncology and Hematology Department, Mirano AULSS3 Serenissima, 30035 Mirano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Scollo","sequence":"additional","affiliation":[{"name":"Division of Gynecology and Obstetrics, Maternal and Child Department, Cannizzaro Hospital, Kore University Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppa","family":"Scandurra","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Cannizzaro Hospital, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Parisi","sequence":"additional","affiliation":[{"name":"Clinica Oncologica e Centro Regionale di Genetica Oncologica, Azienda Ospedaliero-Universitaria delle Marche, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"},{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Artioli","sequence":"additional","affiliation":[{"name":"Oncology Department, Ca\u2019 Foncello Hospital, 31100 Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Innocenza","family":"Palaia","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Vertechy","sequence":"additional","affiliation":[{"name":"Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Bergamini","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Picardo","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynaecology 4, Sant\u2019Anna Hospital, AOU Citt\u00e0 della Salute e della Scienza of Turin, 88100 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7377-0888","authenticated-orcid":false,"given":"Valentina","family":"Tuninetti","sequence":"additional","affiliation":[{"name":"Medical Oncology, Ordine Mauriziano Hospital, 10128 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Scotto","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Scambia","sequence":"additional","affiliation":[{"name":"Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Life Sciences and Public Health, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8836-2633","authenticated-orcid":false,"given":"Sandro","family":"Pignata","sequence":"additional","affiliation":[{"name":"Department of Urology and Gynecology, National Cancer Institute IRCCS Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5444-6305","authenticated-orcid":false,"given":"Giorgio","family":"Valabrega","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Turin, 10124 Turin, Italy"},{"name":"Medical Oncology, Ordine Mauriziano Hospital, 10128 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.20892\/j.issn.2095-3941.2016.0084","article-title":"Epidemiology of ovarian cancer: A review","volume":"14","author":"Reid","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1056\/NEJMoa1810858","article-title":"Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer","volume":"379","author":"Moore","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1056\/NEJMoa1910962","article-title":"Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer","volume":"381","author":"Pothuri","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1056\/NEJMoa1911361","article-title":"Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer","volume":"381","author":"Pautier","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/annonc\/mdq352","article-title":"Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: Outcomes in the partially platinum-sensitive (platinum-free interval 6\u201312 months) subpopulation of OVA-301 phase III randomized trial","volume":"22","author":"Poveda","year":"2011","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1200\/JCO.2009.25.4037","article-title":"Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer","volume":"28","author":"Monk","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1038\/s41416-022-02108-7","article-title":"INOVATYON\/ENGOT-ov5 study: Randomized phase III international study comparing trabectedin\/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin\/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line","volume":"128","author":"Ottevanger","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e658","DOI":"10.1002\/onco.13630","article-title":"A European, Observational, Prospective Trial of Trabectedin Plus Pegylated Liposomal Doxorubicin in Patients with Platinum-Sensitive Ovarian Cancer","volume":"26","author":"Pignata","year":"2021","journal-title":"Oncologist"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"689829","DOI":"10.3389\/fonc.2021.689829","article-title":"The Role of PARP Inhibitors in the Ovarian Cancer Microenvironment: Moving Forward from Synthetic Lethality","volume":"11","author":"Turinetto","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mart\u00ed, J.M., Fern\u00e1ndez-Cort\u00e9s, M., Serrano-S\u00e1enz, S., Zamudio-Martinez, E., Delgado-Bellido, D., Garcia-Diaz, A., and Oliver, F.J. (2020). The Multifactorial Role of PARP-1 in Tumor Microenvironment. Cancers, 12.","DOI":"10.3390\/cancers12030739"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41698-021-00189-w","article-title":"PARP inhibitors promote stromal fibroblast activation by enhancing CCL5 autocrine signaling in ovarian cancer","volume":"5","author":"Li","year":"2021","journal-title":"NPJ Precis Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1136\/ijgc-2022-004149","article-title":"Poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer: Lessons learned and future directions","volume":"33","author":"Caruso","year":"2023","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1136\/ijgc-2022-003543","article-title":"Management of oligometastatic ovarian cancer recurrence during PARP inhibitor maintenance","volume":"32","author":"Palluzzi","year":"2022","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ygyno.2023.04.002","article-title":"Ray-Coquard, PARP inhibitors (PARPi) prolongation after local therapy for oligo-metastatic progression in relapsed ovarian cancer patients","volume":"173","author":"Gauduchon","year":"2023","journal-title":"Gynecol. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41571-021-00532-x","article-title":"Understanding and overcoming resistance to PARP inhibitors in cancer therapy","volume":"18","author":"Dias","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s12943-020-01227-0","article-title":"PARP inhibitor resistance: The underlying mechanisms and clinical implications","volume":"19","author":"Li","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"451","DOI":"10.20517\/cdr.2021.138","article-title":"Ovarian cancer recurrence: \u201cis the definition of platinum resistance modified by PARP inhibitors and other intervening treatments?","volume":"5","author":"Pejovic","year":"2022","journal-title":"\u201d Cancer Drug Resist."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/s41416-023-02326-7","article-title":"PARP inhibitors: Enhancing efficacy through rational combinations","volume":"129","author":"Bhamidipati","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/nature06633","article-title":"Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers","volume":"451","author":"Sakai","year":"2008","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6708","DOI":"10.1158\/1078-0432.CCR-17-0544","article-title":"Diverse BRCA1 and BRCA2 Reversion Mutations in Circulating Cell-Free DNA of Therapy-Resistant Breast or Ovarian Cancer","volume":"23","author":"Weigelt","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1158\/2159-8290.CD-18-0715","article-title":"BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma","volume":"9","author":"Lin","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nature14410","article-title":"Whole\u2013genome characterization of chemoresistant ovarian cancer","volume":"521","author":"Patch","year":"2015","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1200\/JCO.2010.34.2980","article-title":"Secondary Somatic Mutations Restoring BRCA1\/2 Predict Chemotherapy Resistance in Hereditary Ovarian Carcinomas","volume":"29","author":"Norquist","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5578","DOI":"10.1200\/JCO.2023.41.16_suppl.5578","article-title":"Response to subsequent platinum-based chemotherapy post PARP inhibitor in recurrent epithelial ovarian cancer","volume":"41","author":"Vacheresse","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s43032-022-01037-3","article-title":"Platinum Resistance After PARPi Resistance in a gBRCAmt Recurrent Ovarian Cancer Patient: A Case Report","volume":"30","author":"Zhao","year":"2023","journal-title":"Reprod. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.annonc.2022.06.011","article-title":"Efficacy of subsequent chemotherapy for patients with BRCA1\/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: Post-hoc analyses of the SOLO2\/ENGOT Ov-21 trial","volume":"33","author":"Frenel","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ygyno.2019.10.023","article-title":"Olaparib as maintenance therapy in patients with BRCA 1\u20132 mutated recurrent platinum sensitive ovarian cancer: Real world data and post progression outcome","volume":"156","author":"Cecere","year":"2020","journal-title":"Gynecol. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1136\/ijgc-2022-003764","article-title":"Trabectedin plus pegylated liposomal doxorubicin in patients with disease progression after PARP inhibitor maintenance: A real-life case\u2013control study","volume":"33","author":"Vertechy","year":"2023","journal-title":"Int. J. Gynecol. Cancer"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/1\/41\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:42:25Z","timestamp":1760132545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/1\/41"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,20]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["cancers16010041"],"URL":"https:\/\/doi.org\/10.3390\/cancers16010041","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,20]]}}}