title: Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: the MITO 15 trial.
abstract: BACKGROUND
  Current evidence suggest that trabectedin is particularly effective in cells lacking functional homologous recombination repair mechanisms. A prospective phase II trial was designed to evaluate the activity of trabectedin in the treatment of recurrent ovarian cancer patients presenting BRCA mutation and/or BRCAness phenotype.
  
  
  METHODS
  A total of 100 patients with recurrent BRCA-mutated ovarian cancer and/or BRCAness phenotype (≥2 previous responses to platinum) were treated with trabectedin 1.3 mg/mq i.v. q 3 weeks. The activity of the drug with respect to BRCA mutational status and to a series of polymorphisms [single-nucleotide polymorphisms (SNPs)] involved in DNA gene repair was analyzed.
  
  
  RESULTS
  Ninety-four were evaluable for response; in the whole population, 4 complete and 33 partial responses were registered for an overall response rate (ORR) of 39.4. In the platinum-resistant (PR) and -sensitive (PS) population, an ORR of 31.2% and 47.8%, and an overall clinical benefit of 54.2% and 73.9%, respectively, were registered. In the whole series, the median progression-free survival (PFS) was 18 weeks and the median overall survival (OS) was 72 weeks; PS patients showed a more favorable PFS and OS compared with PR patients. BRCA gene mutational status was available in 69 patients. There was no difference in ORR, PFS and OS according to BRCA 1-2 status nor any association between SNPs of genes involved in DNA repair and NER machinery and response to trabectedin was reported.
  
  
  CONCLUSIONS
  Our data prospectively confirmed that the signature of 'repeated platinum sensitivity' identifies patients highly responsive to trabectedin. In this setting, the activity of trabectedin seems comparable to what could be obtained using platinum compounds and the drug may represent a valuable alternative option in patients who present contraindication to receive platinum.
  2011-001298-17.
authors.affiliation: Gynecologic Oncology Unit, Fondazione IRCCS National Cancer Institute, Milan domenica.lorusso@istitutotumori.mi.it.
authors.forename: D
authors.initials: D
authors.lastname: Lorusso
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of Rome.
authors.forename: G
authors.initials: G
authors.lastname: Scambia
authors.affiliation: Department of Gynecologic and Urologic Oncology, Fondazione Pascale, National Cancer Institute of Naples.
authors.forename: S
authors.initials: S
authors.lastname: Pignata
authors.affiliation: Department of Oncology, CRO Aviano, Aviano.
authors.forename: R
authors.initials: R
authors.lastname: Sorio
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of Rome.
authors.forename: G
authors.initials: G
authors.lastname: Amadio
authors.affiliation: Gynecologic Oncology Unit, Fondazione IRCCS National Cancer Institute, Milan.
authors.forename: S
authors.initials: S
authors.lastname: Lepori
authors.affiliation: Medical Oncology Unit, University Hospital S. Maria della Misericordia, Perugia.
authors.forename: A
authors.initials: A
authors.lastname: Mosconi
authors.affiliation: Department of Gynecologic and Urologic Oncology, Fondazione Pascale, National Cancer Institute of Naples.
authors.forename: C
authors.initials: C
authors.lastname: Pisano
authors.affiliation: Department of Obstetrics and Gynecology, San Raffaele Hospital, Milan.
authors.forename: G
authors.initials: G
authors.lastname: Mangili
authors.affiliation: Gynecologic Oncology Unit, Fondazione IRCCS National Cancer Institute, Milan.
authors.forename: G
authors.initials: G
authors.lastname: Maltese
authors.affiliation: Department of Oncology Haematology and Respiratory Disease, AOU Policlinico di Modena, Modena.
authors.forename: R
authors.initials: R
authors.lastname: Sabbatini
authors.affiliation: Medical Oncology Unit, Hospital of Mirano, Mirano.
authors.forename: G
authors.initials: G
authors.lastname: Artioli
authors.affiliation: Medical Oncology Unit, Hospital 'SS. Trinità', Sora.
authors.forename: T
authors.initials: T
authors.lastname: Gamucci
authors.affiliation: Department of Gynecologic and Urologic Oncology, Fondazione Pascale, National Cancer Institute of Naples.
authors.forename: M
authors.initials: M
authors.lastname: Di Napoli
authors.affiliation: Department of Molecular Biology, Catholic University of Rome.
authors.forename: E
authors.initials: E
authors.lastname: Capoluongo
authors.affiliation: Molecular Biology Unit, University Hospital S. Maria della Misericordia, Perugia, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Ludovini
authors.affiliation: Gynecologic Oncology Unit, Fondazione IRCCS National Cancer Institute, Milan.
authors.forename: F
authors.initials: F
authors.lastname: Raspagliesi
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of Rome.
authors.forename: G
authors.initials: G
authors.lastname: Ferrandina
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D004149:Dioxoles / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D017671:Platinum Compounds / Q000627:therapeutic use; D011446:Prospective Studies; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D000077606:Trabectedin
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004149:Dioxoles; D017671:Platinum Compounds; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin
keywords: BRCA; ovarian cancer; trabectedin