886PD - Trabectedin in patients with BRCA mutated and BRCAness phenotype advanced ovarian cancer (AOC): Phase II prospective MITO-15 study

Date 28 September 2014
Event ESMO 2014
Session Gynaecological cancers
Topics Anticancer Agents
Ovarian Cancer
Biological Therapy
Presenter Domenica Lorusso
Citation Annals of Oncology (2014) 25 (suppl_4): iv305-iv326. 10.1093/annonc/mdu338
Authors D. Lorusso1, G. Ferrandina2, S. Pignata3, R. Sorio4, G. Amadio5, A.M. Mosconi6, C. Pisano3, G. Mangili7, C. Masini8, G. Artioli9, F. Narducci10, M. Di Napoli11, C. Rigamonti12, F. Raspagliesi13, G. Scambia14
  • 1Gynaecologic Oncology, National Cancer Institute of Milan, 20133 - Milan/IT
  • 2Gynecologic Oncology, Catholic University, Rome/IT
  • 3Divisione Oncologia Medica A, Istituto Nazionale Tumori di Napoli, 80131 - Napoli/IT
  • 4Medical Oncology, Centro Di Riferimento Oncologico Istituto Nazionale Tumori di Aviano, Aviano/IT
  • 5Gynecologic Oncology, Policlinico Gemelli Catholic University, Rome/IT
  • 6S.c. Oncologia -dep. Onco-ematologia, Ospedale S. Maria della Misericordia, IT-06156 - Perugia/IT
  • 7Medical Oncology, Istituto Scientifico Universitario San Raffaele di Milano, Milan/IT
  • 8Dipartimento Di Oncologia, Ematologia E Malattie Dell’apparato Respiratorio, Centro Oncologico Modenese, Azienda Universitaria Policlinico di Modena, 41214 - Modena/IT
  • 9Medical Oncology, Unita Locale Socio Sanitaria 13 P.O Mirano, Mirano/IT
  • 10Ospedale Ss Trinità, U.O.C. Oncologia Medica, Sora/IT
  • 11Divisione Oncologia Medica A, Istituto Nazionale Tumori Pascale di Napoli, 80131 - Napoli/IT
  • 12Medical Affairs, PharmaMar, 20157 - Milan/IT
  • 13Department Of Gynaecologic Oncology, National Cancer Institute of Milan, 20133 - Milan/IT
  • 14Department Of Gynecologic Oncology, Catholic University, Rome/IT



Trabectedin (Yondelis®) is a minor groove DNA binding agent with suggested activity in patients with defective homologous recombinant DNA repair. This prospective phase II study was designed to evaluate activity of trabectedin in patients with BRCA mutated and BRCAness phenotype AOC (EudraCT N: 2011-001298-17).


AOC patients with documented BRCA mutation or BRCAness phenotype, defined as having had at least 2 previous responses to platinum therapy, were treated with trabectedin 1.3 mg/m2 as a 3-hour i.v. infusion every 3 weeks until disease progression. According to the platinum sensitivity at the time of enrollment, patients were stratified in platinum resistant (PR, <3 platinum responses) or platinum-sensitive (PS, ≥3 previous platinum responses).


A total of 100 patients were enrolled and 88 were evaluable for response (46 PR, 42 PS) after a median follow up of 6 months (range: 1.5-20). Patients had a median age of 59 years (range 49-73); most had serous-papillary histology (86%) and 60% were grade 3. Patients were pretreated with a median of 4 (range 2-14) prior chemotherapy lines and received a median of 6 (range 1-15) trabectedin cycles with a median cumulative dose of 11.0 mg/m2 (range 1.9-30). In the whole population ORR was 41%, median PFS 4.5 months, while median OS was not reached (NR). Patients with BRCA mutations (n = 7), achieved 4 PR (57.1%), 1 SD and 2 PD. Among 518 administered cycles the most frequent grade 3/4 toxicities were neutropenia 17.3%, leukopenia 7.7% and elevation of liver aminotransferases 5.2%. Evaluation of responses according to BRCA mutational status, expression profiling and DNA polymorphisms of genes involved in DNA repair is still ongoing.


Conclusion: Trabectedin represents a valid treatment option in patients with platinum-sensitive AOC and documented BRCA mutation or BRCAness phenotype after multiple platinum lines.

PD Median PFS (months) Median OS (months)
n=46 (%)
15 (32.6) 0 15 (32.6) 12 (26.1) 27 (58.7%) 19 (41.3) 2.7 10
n=42 (%)
21 (50) 4 (9.5) 17 (40.5) 10 (23.8) 31 (73.8%) 11 (26.2) 6 NR

ORR, overall response rate; CR, complete response; PR, partial response; SD, stabilization of disease; DRC, disease control rate; PD, progression of disease; PFS, progression-free survival; OS, overall survival; NR, not reached.


C. Rigamonti: I am an employee of PharmaMar, S.A (Grupo Zeltia).

All other authors have declared no conflicts of interest.