DEBIRI and cetuximab (DEBIRITUX) as a secondline treatment for unresectable colorectal liver metastases (UCLM): results of a phase II trial exploring a new sequence

Abstract

Aim: To investigate efficacy and safety of second‐line treatment with Irinotecan‐loaded Drug‐eluting Beads (DEBIRI ) and cetuximab of unresectable colorectal liver metastases. Methods: Patients with the following characteristics were included in the study: unresectable hepatic metastases from colorectal carcinoma (CRC), progression after first line chemotherapy (any type of chemotherapeutic drug and combination was allowed), second line treatment (mandatory), which included for each patient (unregarding the K‐Ras status) two cycles of DEBIRI (using 100‐300 mum beads loaded with Irinotecan at a total dose 200 mg) followed by 12 cycles of cetuximab that was administered weekly at a first dose of 400 mg/m2 and then 250 mg/m2; good performace status (0‐2) and liver functionality (ALT and gamma‐GT not exceeding three times the upper limit of normal, total bilirubin not exceeding 2.5 mg/ml). Data were collected retrospectively and included: tumor response (evaluated monthly for 6 months then every 3 months), KRas status, type and intensity of adverse events, overall survival and progression free survival. Results: 40 patients with liver metastases from CRC were enrolled. The median duration of DEBIRITUX was 4.4 months (range, 4.0‐6.5). All patients received the planned 2 cycles of DEBIRI and a median of 10 (range 8‐12) cycles of cetuximab. The overall response rate was 50% with 4 complete responses (10%) and 16 (40%) partial responses. The most frequent grade 2 adverse events were: post‐embolization syndrome (30%), diarrhea (25%), skin rushes (38%) and asthenia (35%). The retrospective evaluation of KRas status (24 wild type, 16 mutated) showed a significant higher response rate in the group of patients with wild type KRas. After a median follow‐up of 29 months (range 8‐ 48 months), the median progression‐free survival (PFS) and overall survival (OS) were 9.8 months and 20.4 months, respectively. Future randomized studies are needed in this setting to establish a role for locoregional treatment plus targeted agents compared with systemic chemotherapy. Conclusion: The DEBIRITUX regimen appears to be effective and feasible in second line treatment of unresectable liver metastases from CRC.