TY - JOUR
T1 - Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: Predictive value of DNA-PK and phosphorylated ACC
AU - Perrone, Francesco
AU - Baldassarre, Gustavo
AU - Indraccolo, Stefano
AU - Signoriello, Simona
AU - Chiappetta, Gennaro
AU - Esposito, Franca
AU - Ferrandina, Gabriella
AU - Franco, Renato
AU - Mezzanzanica, Delia
AU - Sonego, Maura
AU - Zulato, Elisabetta
AU - Zannoni, Gian Franco
AU - Canzonieri, Vincenzo
AU - Scambia, Giovanni
AU - Sorio, Roberto
AU - Savarese, Antonella
AU - Breda, Enrico
AU - Scollo, Paolo
AU - Ferro, Antonella
AU - Tamberi, Stefano
AU - Febbraro, Antonio
AU - Natale, Donato
AU - Di Maio, Massimo
AU - Califano, Daniela
AU - Scognamiglio, Giosue'
AU - Lorusso, Domenica
AU - Canevari, Silvana
AU - Losito, Simona
AU - Gallo, Ciro
AU - Pignata, Sandro
PY - 2016
Y1 - 2016
N2 - Background: No biomarker is available to predict prognosis of patients with advanced ovarian cancer (AOC) and guide the choice of chemotherapy. We performed a prospective-retrospective biomarker study within the MITO2 trial on the treatment of AOC. Patients and methods: MITO2 is a randomised multicentre phase 3 trial conducted with 820 AOC patients assigned carboplatin/paclitaxel (carboplatin: AUC5, paclitaxel: 175 mg/m2, every 3 weeks for 6 cycles) or carboplatin/PLD-pegylated liposomal doxorubicin (carboplatin: AUC5, PLD: 30 mg/m2, every 3 weeks for 6 cycles) as first line treatment. Sixteen biomarkers (pathways of adhesion/invasion, apoptosis, transcription regulation, metabolism, and DNA repair) were studied in 229 patients, in a tissue microarray. Progression-free and overall survival were analysed with multivariable Cox model. Results: After 72 months median follow-up, 594 progressions and 426 deaths were reported; there was no significant difference between the two arms in the whole trial. No biomarker had significant prognostic value. Statistically significant interactions with treatment were found for DNA-dependent protein kinase (DNA-PK) and phosphorylated acetyl-coenzymeA carboxylase (pACC), both predicting worse outcome for patients receiving carboplatin/paclitaxel. Conclusion: These data show that in presence of DNA-PK or pACC overexpression, carboplatin/paclitaxel might be less effective than carboplatin/PLD as first line treatment of ovarian cancer patients. Further validation of these findings is warranted.
AB - Background: No biomarker is available to predict prognosis of patients with advanced ovarian cancer (AOC) and guide the choice of chemotherapy. We performed a prospective-retrospective biomarker study within the MITO2 trial on the treatment of AOC. Patients and methods: MITO2 is a randomised multicentre phase 3 trial conducted with 820 AOC patients assigned carboplatin/paclitaxel (carboplatin: AUC5, paclitaxel: 175 mg/m2, every 3 weeks for 6 cycles) or carboplatin/PLD-pegylated liposomal doxorubicin (carboplatin: AUC5, PLD: 30 mg/m2, every 3 weeks for 6 cycles) as first line treatment. Sixteen biomarkers (pathways of adhesion/invasion, apoptosis, transcription regulation, metabolism, and DNA repair) were studied in 229 patients, in a tissue microarray. Progression-free and overall survival were analysed with multivariable Cox model. Results: After 72 months median follow-up, 594 progressions and 426 deaths were reported; there was no significant difference between the two arms in the whole trial. No biomarker had significant prognostic value. Statistically significant interactions with treatment were found for DNA-dependent protein kinase (DNA-PK) and phosphorylated acetyl-coenzymeA carboxylase (pACC), both predicting worse outcome for patients receiving carboplatin/paclitaxel. Conclusion: These data show that in presence of DNA-PK or pACC overexpression, carboplatin/paclitaxel might be less effective than carboplatin/PLD as first line treatment of ovarian cancer patients. Further validation of these findings is warranted.
KW - DNA-PK
KW - Oncology
KW - Ovarian cancer
KW - PACC
KW - Phase 3 clinical trial
KW - Predictive factors
KW - DNA-PK
KW - Oncology
KW - Ovarian cancer
KW - PACC
KW - Phase 3 clinical trial
KW - Predictive factors
UR - http://hdl.handle.net/10807/91774
UR - http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5b%5d=12056&path%5b%5d=38150
U2 - 10.18632/oncotarget.12056
DO - 10.18632/oncotarget.12056
M3 - Article
SN - 1949-2553
VL - 7
SP - 72654
EP - 72661
JO - Oncotarget
JF - Oncotarget
ER -