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

Francesco Perrone, Gustavo Baldassarre, Stefano Indraccolo, Simona Signoriello, Gennaro Chiappetta, Francesca Esposito, Gabriella Ferrandina, Renato Franco, Delia Mezzanzanica, Maura Sonego, Elisabetta Zulato, Gian Franco Zannoni, Vincenzo Canzonieri, Giovanni Scambia, Roberto Sorio, Antonella Savarese, Enrico Breda, P. Scollo, Antonella Ferro, Stefano TamberiAntonio Febbraro, D. Natale, Massimo Di Maio, Daniela Califano, Giosuè Scognamiglio, Domenica Lorusso, Sitvana Canevari, Nunzia Simona Losito, Ciro Gallo, Sandro Pignata

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)72654-72661
Number of pages8
JournalOncotarget
Volume7
Issue number45
DOIs
Publication statusPublished - 2016

Fingerprint

DNA-Activated Protein Kinase
Carboplatin
Ovarian Neoplasms
Biomarkers
Paclitaxel
Therapeutics
Proportional Hazards Models
DNA Repair
Disease-Free Survival
Retrospective Studies
Apoptosis
Drug Therapy

Keywords

  • DNA-PK
  • Ovarian cancer
  • PACC
  • Phase 3 clinical trial
  • Predictive factors

ASJC Scopus subject areas

  • Oncology

Cite this

Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer : Predictive value of DNA-PK and phosphorylated ACC. / Perrone, Francesco; Baldassarre, Gustavo; Indraccolo, Stefano; Signoriello, Simona; Chiappetta, Gennaro; Esposito, Francesca; Ferrandina, Gabriella; Franco, Renato; Mezzanzanica, Delia; Sonego, Maura; Zulato, Elisabetta; Zannoni, Gian Franco; Canzonieri, Vincenzo; Scambia, Giovanni; Sorio, Roberto; Savarese, Antonella; Breda, Enrico; Scollo, P.; Ferro, Antonella; Tamberi, Stefano; Febbraro, Antonio; Natale, D.; Di Maio, Massimo; Califano, Daniela; Scognamiglio, Giosuè; Lorusso, Domenica; Canevari, Sitvana; Losito, Nunzia Simona; Gallo, Ciro; Pignata, Sandro.

In: Oncotarget, Vol. 7, No. 45, 2016, p. 72654-72661.

Research output: Contribution to journalArticle

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, NS, Gallo, C & Pignata, S 2016, 'Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: Predictive value of DNA-PK and phosphorylated ACC', Oncotarget, vol. 7, no. 45, pp. 72654-72661. https://doi.org/10.18632/oncotarget.12056
Perrone, Francesco ; Baldassarre, Gustavo ; Indraccolo, Stefano ; Signoriello, Simona ; Chiappetta, Gennaro ; Esposito, Francesca ; Ferrandina, Gabriella ; Franco, Renato ; Mezzanzanica, Delia ; Sonego, Maura ; Zulato, Elisabetta ; Zannoni, Gian Franco ; Canzonieri, Vincenzo ; Scambia, Giovanni ; Sorio, Roberto ; Savarese, Antonella ; Breda, Enrico ; Scollo, P. ; Ferro, Antonella ; Tamberi, Stefano ; Febbraro, Antonio ; Natale, D. ; Di Maio, Massimo ; Califano, Daniela ; Scognamiglio, Giosuè ; Lorusso, Domenica ; Canevari, Sitvana ; Losito, Nunzia Simona ; Gallo, Ciro ; Pignata, Sandro. / Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer : Predictive value of DNA-PK and phosphorylated ACC. In: Oncotarget. 2016 ; Vol. 7, No. 45. pp. 72654-72661.
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T1 - Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer

T2 - 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, Francesca

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, P.

AU - Ferro, Antonella

AU - Tamberi, Stefano

AU - Febbraro, Antonio

AU - Natale, D.

AU - Di Maio, Massimo

AU - Califano, Daniela

AU - Scognamiglio, Giosuè

AU - Lorusso, Domenica

AU - Canevari, Sitvana

AU - Losito, Nunzia 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.

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KW - Predictive factors

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