PMID- 38315944 OWN - NLM STAT- MEDLINE DCOM- 20240426 LR - 20240426 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 42 IP - 13 DP - 2024 May 1 TI - Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. PG - 1488-1498 LID - 10.1200/JCO.23.01225 [doi] AB - PURPOSE: Literature evidence suggests that trabectedin monotherapy is effective in patients with recurrent ovarian cancer (OC) presenting BRCA mutation and/or BRCAness phenotype. METHODS: A prospective, open-label, randomized phase III MITO-23 trial evaluated the activity and safety of trabectedin 1.3 mg/m(2) given once every 3 weeks (arm A) in BRCA 1/2 mutation carriers or patients with BRCAness phenotype (ie, patients who responded to >/=two previous platinum-based treatments) with recurrent OC, primary peritoneal carcinoma, or fallopian tube cancer in comparison with physician's choice chemotherapy in the control arm (arm B; pegylated liposomal doxorubicin, topotecan, gemcitabine, once-weekly paclitaxel, or carboplatin). The primary end point was overall survival (OS) evaluated in the intention-to-treat population. RESULTS: Overall, 244 patients from 21 MITO centers were randomly assigned (arm A = 122/arm B = 122). More than 70% of patients received >/=three previous chemotherapy lines and 35.7% had received a poly (ADP-ribose) polymerase inhibitor (PARPi) before enrollment. Median OS was not significantly different between the arms: arm A: 15.8 versus arm B: 17.9 months (P = .304). Median progression-free survival was 4.9 months in arm A versus 4.4 months in arm B (P = .897). Among 208 patients evaluable for efficacy, the objective response rate was 17.1% in arm A and 21.4% in arm B, with comparable median duration of response (5.62 v 5.66 months, respectively). No superior effect was observed for trabectedin in the prespecified subgroup analyses according to BRCA mutational status, chemotherapy type, and pretreatment with a PARPi and/or platinum-free interval. Trabectedin showed a higher frequency of grade >/=3 adverse events (AEs), serious AEs, and serious adverse drug reactions compared with control chemotherapy. CONCLUSION: Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy. FAU - Lorusso, Domenica AU - Lorusso D AUID- ORCID: 0000-0003-0981-0598 AD - Fondazione Policlinico Universitario A. Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy. FAU - Raspagliesi, Francesco AU - Raspagliesi F AD - Fondazione IRCCS Istituto Nazionale Tumori Milan, Milan, Italy. FAU - Ronzulli, Dominique AU - Ronzulli D AD - Fondazione IRCCS Istituto Nazionale Tumori Milan, Milan, Italy. FAU - Valabrega, Giorgio AU - Valabrega G AUID- ORCID: 0000-0001-5444-6305 AD - Department of Oncology, Oncology Unit, University of Turin, Ordine Mauriziano Hospital, Turin, Italy. FAU - Colombo, Nicoletta AU - Colombo N AUID- ORCID: 0000-0003-2225-715X AD - European Institute of Oncology IRCCS and Universita degli Studi di Milano Bicocca, Milan, Italy. FAU - Pisano, Carmela AU - Pisano C AUID- ORCID: 0000-0003-4577-6534 AD - Department of Urology and Gynecology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione G. Pascale, Naples, Italy. FAU - Cassani, Chiara AU - Cassani C AUID- ORCID: 0000-0002-8055-5086 AD - Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, Unit of Obstetrics and Gynecology, University of Pavia, IRCCS San Matteo Hospital Foundation, Pavia, Italy. FAU - Tognon, Germana AU - Tognon G AUID- ORCID: 0000-0003-3935-4992 AD - ASST Spedali Civili di Brescia, Universita di Brescia, Brescia, Italy. FAU - Tamberi, Stefano AU - Tamberi S AD - Ospedale degli Infermi-AUSL, Ravenna, Italy. FAU - Mangili, Giorgia AU - Mangili G AD - IRCCS San Raffaele Hospital, Milan, Italy. FAU - Mammoliti, Serafina AU - Mammoliti S AUID- ORCID: 0000-0002-6560-0061 AD - IRCCS Ospedale Policlinico San Martino, Genova, Italy. FAU - De Giorgi, Ugo AU - De Giorgi U AUID- ORCID: 0000-0001-7520-2908 AD - IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy. FAU - Greco, Filippo AU - Greco F AD - Oncology Unit, Mater Salutis Hospital, Ulss 9 Veneto Region, Legnago, Italy. FAU - Mosconi, Anna Maria AU - Mosconi AM AUID- ORCID: 0000-0002-5386-6049 AD - Azenda Ospedaliera Perugia, Perugia, Italy. FAU - Breda, Enrico AU - Breda E AUID- ORCID: 0000-0001-5274-5379 AD - MITO and Fatebenefratelli Hospital, Rome, Italy. FAU - Artioli, Grazia AU - Artioli G AD - Ulss 2 Marca Trevigiana, Treviso, Italy. FAU - Andreetta, Claudia AU - Andreetta C AUID- ORCID: 0000-0002-0470-043X AD - Department of Oncology, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy. FAU - Casanova, Claudia AU - Casanova C AD - Department of Oncology, Ospedale Civile Santa Maria delle Croci, Ravenna, Italy. FAU - Ceccherini, Rita AU - Ceccherini R AD - Department of Oncology, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, Italy. FAU - Frassoldati, Antonio AU - Frassoldati A AUID- ORCID: 0000-0003-3487-3259 AD - S Anna University Hospital, Ferrara, Italy. FAU - Salutari, Vanda AU - Salutari V AD - Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. FAU - Giolitto, Serena AU - Giolitto S AD - Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. FAU - Scambia, Giovanni AU - Scambia G AUID- ORCID: 0000-0002-9503-9041 AD - Fondazione Policlinico Universitario A. Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy. LA - eng SI - ClinicalTrials.gov/NCT02903004 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 - 20240205 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - ID0YZQ2TCP (Trabectedin) RN - 0 (BRCA1 protein, human) RN - 0 (BRCA2 protein, human) RN - 0 (BRCA2 Protein) RN - 0 (BRCA1 Protein) RN - 0 (Antineoplastic Agents, Alkylating) SB - IM MH - Humans MH - Female MH - *Trabectedin/therapeutic use/administration & dosage MH - Middle Aged MH - *Ovarian Neoplasms/drug therapy/genetics/mortality MH - Aged MH - Adult MH - *Mutation MH - *Neoplasm Recurrence, Local/drug therapy MH - Phenotype MH - Prospective Studies MH - BRCA2 Protein/genetics MH - BRCA1 Protein/genetics MH - Antineoplastic Agents, Alkylating/therapeutic use/adverse effects/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects MH - Aged, 80 and over MH - Progression-Free Survival EDAT- 2024/02/05 18:42 MHDA- 2024/04/27 09:50 CRDT- 2024/02/05 16:03 PHST- 2024/04/27 09:50 [medline] PHST- 2024/02/05 18:42 [pubmed] PHST- 2024/02/05 16:03 [entrez] AID - 10.1200/JCO.23.01225 [doi] PST - ppublish SO - J Clin Oncol. 2024 May 1;42(13):1488-1498. doi: 10.1200/JCO.23.01225. Epub 2024 Feb 5.