According to the results of a Phase II study published early online in Lancet Oncology, the addition of cetuximab to standard neoadjuvant chemotherapy for unresectable colorectal liver metastases increased the proportion of lesions that were rendered eligible for curative resection.

A total of 114 patients with non-resectable liver metastases (technically non-resectable or ≥5 metastases) were randomised (non-blinded) to receive cetuximab in addition to FOLFOX6 (oxaliplatin, fluorouracil, and folinic acid; group A, n=56) or FOLFIRI (irinotecan, fluorouracil, and folinic acid; group B, n=55). Tumour response (primary endpoint) was evaluated every 8 weeks (CT or MRI) and resectability was reassessed after 16 weeks and then every 2 months up to 2 years.  Patients with resectable disease were offered liver surgery within 4—6 weeks of the last treatment cycle.

Three patients were excluded from the primary endpoint analysis; two as they discontinued prior to receiving the first full dose, and one because of early pulmonary embolism.  The main findings were as follows (As reported in the abstract):

• A confirmed partial or complete response was noted in 36 (68%) of 53 patients in group A, and 30 (57%) of 53 patients in group B (difference 11%, 95% CI −8 to 30; odds ratio [OR] 1.62, 0.74—3.59; p=0.23).

• In a retrospective analysis of response by KRAS status, a partial or complete response was noted in 47 (70%) of 67 patients with KRAS wild-type tumours versus 11 (41%) of 27 patients with KRAS-mutated tumours (OR 3.42, 1.35—8.66; p=0.0080).

• R0 resection was done in 20 (38%) of 53 patients in group A and 16 (30%) of 53 of patients in group B.

• A retrospective, blinded surgical review of patients with radiological images at both baseline and during treatment was done to assess objectively any changes in resectability.  According to this, resectability rates increased from 32% at baseline to 60% after chemotherapy (p<0.0001).

• The most frequent grade 3 and 4 toxicities were skin toxicity and neutropenia.