Liver metastases in advanced colorectal cancer are more likely to shrink to an operable size when cetuximab is added to a patient’s neoadjuvant therapy, a study published Online First in The Lancet Oncology reports.
The 10-year survival rate for people whose colorectal liver metastases (CLM) are rendered secondarily resectable is close to that for people whose tumours are initially respectable, so tumour shrinkage is an important goal. Researchers investigated the effect on CLM resectability of adding the monoclonal antibody cetuximab to neoadjuvant chemotherapy.
Between December 2004 and March 2008 the authors randomised 109 patients to one of two regimens: cetuximab plus FOLFOX6 (oxaliplatin, fluorouracil and folinic acid); or cetuximab plus FOLFIRI (irinotecan, fluorouracil and folinic acid). Every 8 weeks – four treatment cycles – they assessed CLM response to treatment, and resectability, using CT or MRI scans. If the tumours were assessed as being resectable, patients were offered liver surgery.
Seven surgeons undertook blinded surgical reviews of two-thirds of the scan images, at baseline and during treatment, to assess objectively how resectability changed.
In the FOLFOX6 group of patients, 68% of patients had a complete or partial tumour response; this figure was 57% for the FOLFIRI group. As found in previous studies, tumours were more likely to respond if patients had KRAS wild-type tumours than if they had KRAS tumour mutations (70% versus 41%) because the mutation confers cetuximab resistance.
After treatment with cetuximab, there was a significant increase in the proportion of tumours that were deemed resectable on blinded review – from 32% at the start of the study to 60% after chemotherapy.
Almost three-quarters (72%) of patients experienced grade 3 toxicity, most commonly skin reactions and neutropenia.
Authors of the accompanying comment welcome the 70% response rate for wild-type tumours as “very encouraging” and ask for further trials comparing the effects on survival of different biologicals combined with chemotherapy.
