Perioperative Triplet Chemotherapy and Cetuximab in Patients WithRASWild Type High Recurrence Risk or Borderline Resectable Colorectal Cancer Liver Metastases

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For borderline resectable colorectal cancer liver metastases (CLM), systemic treatment can help to achieve R0 resection and reduce the risk of relapse. We assessed the role of perioperative triplet chemotherapy in combination with cetuximab in patients with RAS wild type high recurrence risk and/or borderline resectable CLM.

Patients and Methods:

This was a monocenter, open-label phase II study. Borderline resectability was defined technically as tumor involvement of >1 hepatic vein, or >4 hepatic segments, need for 2-stage hepatectomy or radiofrequency ablation, and/or biologically (high risk): ≥4 metastatic nodules, or synchronous metastases. Patients were treated with 4 pre- and postoperative cycles of biweekly COI-E (cetuximab 500 mg/m2 and irinotecan 180 mg/m2 on day 1, oxaliplatin 85 mg/m2 on day 2, and capecitabine 1000 mg/m2 twice per day on days 2-6). The primary end point was overall response rate.


Forty patients were enrolled. Nine patients with KRAS mutation were excluded after amendment in 2010. In an extended RAS test we did not find additional RAS mutations. The final population was comprised of 31 patients with RAS wild type CLM (technically borderline resectable 39%; synchronous 84%; ≥4 metastatic nodules 29%). The overall response, R0 resection, and pathological response rates were 87%, 84%, and 33%, respectively. At a median follow-up of 4 years, median progression-free survival and overall survival were 17.8 and 62.5 months, respectively. Treatment toxicity was relevant but did not jeopardize the surgical plan.


The COI-E regimen was associated with high response and R0 resection rates in patients with RAS wild type CLM with borderline resectability and/or high-risk features.

In this phase II trial we aimed to evaluate the activity and safety of early resection with perioperative triplet chemotherapy in combination with cetuximab in 31 patients with high recurrence risk and/or borderline resectableRASwild type colorectal cancer liver metastases. The results showed a high response rate (87%), depth of response (−51%), and R0 resection (83%), with manageable toxicity. Perioperative triplet chemotherapy in combination with cetuximab was a feasible strategy in this setting and should be further evaluated for unresectable or technically borderline resectableRASandBRAFwild type colorectal cancer.

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