D Lorusso1, G Scambia2, S Pignata3, R Sorio4, G Amadio2, S Lepori5, A Mosconi6, C Pisano3, G Mangili7, G Maltese5, R Sabbatini8, G Artioli9, T Gamucci10, M Di Napoli3, E Capoluongo11, V Ludovini12, F Raspagliesi5, G Ferrandina2. 1. Gynecologic Oncology Unit, Fondazione IRCCS National Cancer Institute, Milan domenica.lorusso@istitutotumori.mi.it. 2. Department of Obstetrics and Gynecology, Catholic University of Rome. 3. Department of Gynecologic and Urologic Oncology, Fondazione Pascale, National Cancer Institute of Naples. 4. Department of Oncology, CRO Aviano, Aviano. 5. Gynecologic Oncology Unit, Fondazione IRCCS National Cancer Institute, Milan. 6. Medical Oncology Unit, University Hospital S. Maria della Misericordia, Perugia. 7. Department of Obstetrics and Gynecology, San Raffaele Hospital, Milan. 8. Department of Oncology Haematology and Respiratory Disease, AOU Policlinico di Modena, Modena. 9. Medical Oncology Unit, Hospital of Mirano, Mirano. 10. Medical Oncology Unit, Hospital 'SS. Trinità', Sora. 11. Department of Molecular Biology, Catholic University of Rome. 12. Molecular Biology Unit, University Hospital S. Maria della Misericordia, Perugia, Italy.
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.
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 cancerpatients 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; PSpatients 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.
Authors: Marilena Di Napoli; Chiara Della Pepa; Laura Arenare; Giovanni Scambia; Domenica Lorusso; Francesco Raspagliesi; Gabriella Ferrandina; Vanda Salutari; Roberto Sorio; Anna Maria Mosconi; Giorgia Mangili; Lucia Borgato; Stefano Lepori; Angela Salvino; Sandro Pignata; Sabrina Chiara Cecere Journal: Support Care Cancer Date: 2017-01-19 Impact factor: 3.603
Authors: Giovanni Luca Scaglione; Paola Concolino; Maria De Bonis; Elisa De Paolis; Angelo Minucci; Gabriella Ferrandina; Giovanni Scambia; Ettore Capoluongo Journal: Int J Mol Sci Date: 2018-03-23 Impact factor: 5.923
Authors: Alexander J Cortez; Patrycja Tudrej; Katarzyna A Kujawa; Katarzyna M Lisowska Journal: Cancer Chemother Pharmacol Date: 2017-12-16 Impact factor: 3.333