%0 Clinical Trial, Phase III
%T Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC.
%A Perrone F
%A Baldassarre G
%A Indraccolo S
%A Signoriello S
%A Chiappetta G
%A Esposito F
%A Ferrandina G
%A Franco R
%A Mezzanzanica D
%A Sonego M
%A Zulato E
%A Zannoni GF
%A Canzonieri V
%A Scambia G
%A Sorio R
%A Savarese A
%A Breda E
%A Scollo P
%A Ferro A
%A Tamberi S
%A Febbraro A
%A Natale D
%A Di Maio M
%A Califano D
%A Scognamiglio G
%A Lorusso D
%A Canevari S
%A Losito S
%A Gallo C
%A Pignata S
%J Oncotarget
%V 7
%N 45
%D 11 2016 8
%M 27655643
暂无%R 10.18632/oncotarget.12056
%X 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.<BR>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.<BR>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.<BR>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.