CETUXICOL, a phase II trial randomizing standard treatment with or without cetuximab in primary cervical cancer treatment.

Abstract

e15535 Background: Advanced stage cervical cancer (CC) remains a public health issue despite preventive vaccines and screening. EGFR is over-expressed in 50 to 85% of CC and activated in 20%, suggesting that EGFR blockage may be a promising treatment approach. Methods: A randomized phase 2 trial on 78 stage IB2–III patients from 11 French Cancer Centres evaluated the tolerance and early response to cetuximab, an anti EGFR antibody. 40 patients received cetuximab + standard RT and Cisplatinum based chemotherapy (arm A) and 38 patients received standard treatment (B). Primary endpoint is DFS at 2 years and presently not reached. MRI imaging revealed no difference in median (44 vs 40) tumour sizes between arms; there was no difference in age, menopausal status, PI and smoking habits. Parametrial involvement was clinically diagnosed in 19 and 20 cases respectively. Presence of lumbar or para-aortic lymph nodes was an exclusion criterion. Three patients withdrew consent in the cetuximab arm, one accepted standard treatment. Treatment schedules were incomplete in 13 (A) and 14 (B) patients for reasons of haematological or renal toxicity. Results: Surgical resection was feasible in 24 (65%) and 26 (70%) patients in arms A and B respectively.Tolerance was satisfactory in both arms, with significantly more acne form reactions in the cetuximab arm of grade 2 (n= 19) and 3 (n=4). More patients had diarrhea (n=8 vs 4: ns) associated with nausea and vomiting of grade 3 (n=4) and 4 (n=1) in the cetuximab arm (ns).Early results show a complete response at 6 weeks by MRI in 18% and 8% for arms A and B respectively. A central blinded review of the imaging and pathology slides is presently ongoing. Conclusions: The prediction of a response to EGFR targeted therapy in cervical cancer remains a matter of debate since no precise molecular studies are available. Consequently, no decisive results have been achieved in early trials of non selected patients with late stage disease (GOG 76-DD). Biopsy samples are available for the majority of our patients and analyses of EGFR expression, cellular sub-localization and main mutations in the PI3K pathway are ongoing. Molecular studies to allow hierarchical decision making are warranted in future studies.