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 language | English |
|---|---|
| Article number | mdv608 |
| Pages (from-to) | 487-493 |
| Number of pages | 7 |
| Journal | Annals of Oncology |
| Volume | 27 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 1 2016 |
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Keywords
- BRCA
- Ovarian cancer
- Trabectedin
ASJC Scopus subject areas
- Oncology
- Hematology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients
T2 - The MITO 15 trial
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
PY - 2016/3/1
Y1 - 2016/3/1
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.
KW - BRCA
KW - Ovarian cancer
KW - Trabectedin
UR - http://www.scopus.com/inward/record.url?scp=84959863353&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959863353&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdv608
DO - 10.1093/annonc/mdv608
M3 - Article
VL - 27
SP - 487
EP - 493
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 3
M1 - mdv608
ER -