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

Abstract

BACKGROUND: 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. PATIENTS AND METHODS: ARCC patients, ECOG PS\u202f 64\u202f1, were randomized to CP for 6\u202fcycles with or without CET (400\u202fmg/m2 one week before starting CP, then 250\u202fmg/m2 weekly) until disease progression or unacceptable toxicity. Event-free survival (EFS) was the primary endpoint. With a 4.5\u202fmonths expected median EFS and a 6.4\u202fmonths predicted EFS (HR 0.70), 0.20 one-tailed \u3b1 and 80% power, 89 events were required for the final intent-to-treat analysis. RESULTS: 108 patients were assigned to CP (n\u202f=\u202f53) or CP-CET (n\u202f=\u202f55). 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\u202fmonths, 102 patients had an event, 97 progressed and 61 died. Median EFS was 4.7 and 6.0\u202fmonths (one-tail P\u202f=\u202f0.43), median PFS was 5.2 and 7.6\u202fmonths (one-tail P\u202f=\u202f0.20) and median OS was 17.7 and 17\u202fmonths (one-tail P\u202f=\u202f0.27), 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. CONCLUSION: CP-CET was not more active than CP alone in unselected ARCC patien