Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC.

Abstract

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.

• Authors: Francesco Perrone, Gustavo Baldassarre, Stefano Indraccolo, Simona Signoriello, Gennaro Chiappetta, Franca Esposito, Gabriella Ferrandina, Renato Franco, Delia Mezzanzanica, Maura Sonego, Elisabetta Zulato, Gian F Zannoni, Vincenzo Canzonieri, Giovanni Scambia, Roberto Sorio, Antonella Savarese, Enrico Breda, Paolo Scollo, Antonella Ferro, Stefano Tamberi, Antonio Febbraro, Donato Natale, Massimo Di Maio, Daniela Califano, Giosuè Scognamiglio, Domenica Lorusso, Silvana Canevari, Simona Losito, Ciro Gallo, Sandro Pignata
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 45 Pg. 72654-72661 (11 08 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27655643 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• DNA-Activated Protein Kinase

Topics

• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• DNA-Activated Protein Kinase (genetics)
• Disease-Free Survival
• Female
• Humans
• Ovarian Neoplasms (drug therapy, pathology)
• Prognosis