Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: The MITO 15 trial

Domenica Lorusso, Giovanni Scambia, Sandro Pignata, Roberto Sorio, Giulia Amadio, S. Lepori, A. M. Mosconi, Carmela Pisano, Giorgia Mangili, Giuseppa Maltese, Roberto Sabbatini, G. Artioli, T. Gamucci, Marilena Di Napoli, Ettore Capoluongo, Vienna Ludovini, Francesco Raspagliesi, Gabriella Ferrandina

Research output: Contribution to journalArticle

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. Patients and 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. EudraCT Number: 2011-001298-17.

Original languageEnglish
Article numbermdv608
Pages (from-to)487-493
Number of pages7
JournalAnnals of Oncology
Volume27
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

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trabectedin
Ovarian Neoplasms
Phenotype
Platinum
Disease-Free Survival
DNA Repair
Single Nucleotide Polymorphism
Survival
Platinum Compounds
Genes
Recombinational DNA Repair
Vulnerable Populations

Keywords

  • BRCA
  • Ovarian cancer
  • Trabectedin

ASJC Scopus subject areas

  • Oncology
  • Hematology

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Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients : The MITO 15 trial. / Lorusso, Domenica; Scambia, Giovanni; Pignata, Sandro; Sorio, Roberto; Amadio, Giulia; Lepori, S.; Mosconi, A. M.; Pisano, Carmela; Mangili, Giorgia; Maltese, Giuseppa; Sabbatini, Roberto; Artioli, G.; Gamucci, T.; Di Napoli, Marilena; Capoluongo, Ettore; Ludovini, Vienna; Raspagliesi, Francesco; Ferrandina, Gabriella.

In: Annals of Oncology, Vol. 27, No. 3, mdv608, 01.03.2016, p. 487-493.

Research output: Contribution to journalArticle

Lorusso, D, Scambia, G, Pignata, S, Sorio, R, Amadio, G, Lepori, S, Mosconi, AM, Pisano, C, Mangili, G, Maltese, G, Sabbatini, R, Artioli, G, Gamucci, T, Di Napoli, M, Capoluongo, E, Ludovini, V, Raspagliesi, F & Ferrandina, G 2016, 'Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: The MITO 15 trial', Annals of Oncology, vol. 27, no. 3, mdv608, pp. 487-493. https://doi.org/10.1093/annonc/mdv608
Lorusso, Domenica ; Scambia, Giovanni ; Pignata, Sandro ; Sorio, Roberto ; Amadio, Giulia ; Lepori, S. ; Mosconi, A. M. ; Pisano, Carmela ; Mangili, Giorgia ; Maltese, Giuseppa ; Sabbatini, Roberto ; Artioli, G. ; Gamucci, T. ; Di Napoli, Marilena ; Capoluongo, Ettore ; Ludovini, Vienna ; Raspagliesi, Francesco ; Ferrandina, Gabriella. / Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients : The MITO 15 trial. In: Annals of Oncology. 2016 ; Vol. 27, No. 3. pp. 487-493.
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AU - Lorusso, Domenica

AU - Scambia, Giovanni

AU - Pignata, Sandro

AU - Sorio, Roberto

AU - Amadio, Giulia

AU - Lepori, S.

AU - Mosconi, A. M.

AU - Pisano, Carmela

AU - Mangili, Giorgia

AU - Maltese, Giuseppa

AU - Sabbatini, Roberto

AU - Artioli, G.

AU - Gamucci, T.

AU - Di Napoli, Marilena

AU - Capoluongo, Ettore

AU - Ludovini, Vienna

AU - Raspagliesi, Francesco

AU - Ferrandina, Gabriella

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N2 - 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. Patients and 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. EudraCT Number: 2011-001298-17.

AB - 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. Patients and 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. EudraCT Number: 2011-001298-17.

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