The MITO CERV-2 trial: A randomized phase II study of cetuximab plus carboplatin and paclitaxel, in advanced or recurrent cervical cancer.

Sandro Pignata, Giovanni Scambia, Domenica Lorusso, Ugo De Giorgi, Maria Ornella Nicoletto, Rossella Lauria, Anna Maria Mosconi, Cosimo Sacco, Claudia Omarini, Pierosandro Tagliaferri, Gabriella Ferrandina, Saverio Cinieri, Antonella Savarese, Giorgio Valabrega, Carmela Pisano, Vanda Salutari, Francesco Raspagliesi, Barbara Kopf, Sabrina Chiara Cecere, Giulia AmadioGiuseppa Maltese, Marilena Di Napoli, Stefano Greggi, Simona Signoriello, Gennaro Daniele, Alessandra Sacco, Simona Losito, Nicola Normanno, Francesco Perrone, Ciro Gallo, Maria Carmela Piccirillo, MITO Investigators

Research output: Contribution to journalArticlepeer-review

Abstract

Cervical cancer cells often express Epidermal Growth Factor Receptor (EGFR). Cetuximab (CET), an anti-EGFR antibody, can be safely combined with carboplatin (C) and paclitaxel (P), a standard treatment for advanced/recurrent cervical cancer (ARCC) patients. ARCC patients, ECOG PS ≤ 1, were randomized to CP for 6 cycles with or without CET (400 mg/m one week before starting CP, then 250 mg/m weekly) until disease progression or unacceptable toxicity. Event-free survival (EFS) was the primary endpoint. With a 4.5 months expected median EFS and a 6.4 months predicted EFS (HR 0.70), 0.20 one-tailed α and 80% power, 89 events were required for the final intent-to-treat analysis. 108 patients were assigned to CP (n = 53) or CP-CET (n = 55). Median age was 50, 69% were PS0, 76% had recurrent disease, 91% had distant metastasis and 57% had received previous chemotherapy. After a median follow-up of 23 months, 102 patients had an event, 97 progressed and 61 died. Median EFS was 4.7 and 6.0 months (one-tail P = 0.43), median PFS was 5.2 and 7.6 months (one-tail P = 0.20) and median OS was 17.7 and 17 months (one-tail P = 0.27), with CP and CP-CET, respectively. There was no difference in the occurrence of severe adverse events, except for skin toxicity. Biomarker analysis, in a small subgroup of patients, suggests that PIK3CA mutation might be predictive of CET resistance. CP-CET was not more active than CP alone in unselected ARCC patients.
Original languageUndefined/Unknown
Pages (from-to)535-540
Number of pages6
JournalGynecologic Oncology
Volume153
DOIs
Publication statusPublished - Jun 1 2019

Keywords

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols
  • adverse effects
  • therapeutic use
  • Carboplatin
  • administration & dosage
  • Cetuximab
  • Class I Phosphatidylinositol 3-Kinases
  • genetics
  • Disease Progression
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence
  • Local
  • drug therapy
  • Paclitaxel
  • Progression-Free Survival
  • Prospective Studies
  • Response Evaluation Criteria in Solid Tumors
  • Uterine Cervical Neoplasms
  • Cervical cancer
  • PIK3CA mutation
  • Randomized phase 2

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