title: Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC.
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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione G.Pascale, IRCCS, Napoli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Perrone
authors.affiliation: Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Baldassarre
authors.affiliation: Istituto Oncologico Veneto, IRCCS, Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Indraccolo
authors.affiliation: Dipartimento di Salute Mentale, Fisica e Medicina Preventiva, Statistica Medica, Seconda Università, Napoli, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Signoriello
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione G.Pascale, IRCCS, Napoli, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Chiappetta
authors.affiliation: Università di Napoli Federico II, Napoli, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Esposito
authors.affiliation: Catholic University, Roma, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferrandina
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione G.Pascale, IRCCS, Napoli, Italy.|Dipartimento di Salute mentale, Fisica e Medicina Preventiva, Anatomia Patologica, Seconda Università, Napoli Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Mezzanzanica
authors.affiliation: Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Sonego
authors.affiliation: Istituto Oncologico Veneto, IRCCS, Padova, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Zulato
authors.affiliation: Catholic University, Roma, Italy.
authors.forename: Gian F
authors.initials: GF
authors.lastname: Zannoni
authors.affiliation: Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Canzonieri
authors.affiliation: Catholic University, Roma, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.affiliation: Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sorio
authors.affiliation: Istituto Nazionale Tumori Regina Elena, IRCCS, Roma, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Savarese
authors.affiliation: Ospedale S. Giovanni Calibita Fatebenefratelli, Roma, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Breda
authors.affiliation: Ospedale Cannizzaro, Catania, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Scollo
authors.affiliation: Ospedale S. Chiara, Trento, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Ferro
authors.affiliation: Ospedale Civile, Faenza, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tamberi
authors.affiliation: Ospedale Fatebenefratelli, Benevento, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Febbraro
authors.affiliation: Ospedale S. Massimo, Penne (PE), Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Natale
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione G.Pascale, IRCCS, Napoli, Italy.|Università degli Studi, Torino, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione G.Pascale, IRCCS, Napoli, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Califano
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione G.Pascale, IRCCS, Napoli, Italy.
authors.forename: Giosuè
authors.initials: G
authors.lastname: Scognamiglio
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Lorusso
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione G.Pascale, IRCCS, Napoli, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Losito
authors.affiliation: Dipartimento di Salute Mentale, Fisica e Medicina Preventiva, Statistica Medica, Seconda Università, Napoli, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Gallo
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione G.Pascale, IRCCS, Napoli, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D051747:DNA-Activated Protein Kinase / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis
chemical_list: D051747:DNA-Activated Protein Kinase
keywords: DNA-PK; ovarian cancer; pACC; phase 3 clinical trial; predictive factors