D01* - MITO (Multicentre Italian Trials in Ovarian cancer) - CERV 2 trial: a randomized phase II study of carboplatin and paclitaxel +/- cetuximab, in advanced and/or recurrent cervical cancer

Abstract

Background: Carboplatin (C) plus paclitaxel (P) is among standard options for treatment of advanced or recurrent cervical cancer (ARCC) patients (pts). Cervical cancer cells often express Epidermal Growth Factor receptor (EGFR). Cetuximab (CET), an anti-EGFR monoclonal antibody, can be safely combined with CP. MITO-CERV 2 is a comparative randomized phase 2 study, testing the addition of CET to CP. Methods: ARCC pts, <2 previous chemotherapy, ECOG PS = 1, were randomized to CP (C AUC5 + P 175 mg/m2, d1q21) for 6 cycles +/- CET (400 mg/m2 one week before starting CP, then 250 mg/m2 weekly) until disease progression or unacceptable toxicity. Primary endpoint was event-free survival (EFS), i.e. time from randomization to progression, death, definitive discontinuation of the whole treatment or loss to follow-up, whichever occurred first. With a 4.5 mos expected median EFS and a 6.4 mos auspicated EFS (HR 0.70), 0.20 one-tailed a and 80% power, 89 events were required for the final intent-to-treat analysis. Results: 108 pts were randomly assigned to CP (n = 53) or to 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. A median number of 6 CP cycles was given in both arms. After a median follow-up of 23 mos (95% CI:20-26), 102 pts had an event, 97 progressed and 61 died. Median EFS was 4.7 and 6.0 mos (one-tail p = 0.43), median PFS was 5.2 and 7.6 mos (one-tail p = 0.20) and median OS was 17.7 and 17 mos (one-tail p = 0.27), with CP and CP-CET, respectively. One patient died for a stroke during standard treatment. There was no difference in the occurrence of severe side-effects, except grade 3-4 skin toxicity reported only with CP-CET (8 cases, 6 with acneiform rash, p = 0.004). Out of 86 patients eligible for RECIST, objective response rate was 43% and 38% with CP and CP-CET respectively (p = 0.63). Conclusion: The addition of CET to CP is not worthy of further investigation in unselected ARCC pts. Efforts are ongoing to retrospectively collect tumor samples for an exploratory biomarker analysis. ClinicalTrials.gov NCT00997009. Partially supported by Merck Serono.