{Reference Type}: Clinical Trial, Phase III
{Title}: Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC.
{Author}: Perrone F;Baldassarre G;Indraccolo S;Signoriello S;Chiappetta G;Esposito F;Ferrandina G;Franco R;Mezzanzanica D;Sonego M;Zulato E;Zannoni GF;Canzonieri V;Scambia G;Sorio R;Savarese A;Breda E;Scollo P;Ferro A;Tamberi S;Febbraro A;Natale D;Di Maio M;Califano D;Scognamiglio G;Lorusso D;Canevari S;Losito S;Gallo C;Pignata S;
{Journal}: Oncotarget
{Volume}: 7
{Issue}: 45
{Year}: 11 2016 8
暂无{DOI}: 10.18632/oncotarget.12056
{Abstract}: 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.