EXPAND study shows no benefit from adding cetuximab to the first-line chemotherapy in advanced gastric cancer

Cetuximab in combination with capecitabine and cisplatin in patients with gastric and gastroesophageal junction cancer

EXPAND is a large open-label, randomised, controlled, phase III trial of cetuximab plus capecitabine and cisplatin in patients with advanced gastric cancer, which has a poor prognosis and no established standard treatment. The results from the study do not show a benefit from adding cetuximab. The study data are reported by Dr Florian Lordick at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.

The current trial compared capecitabine and cisplatin with and without anti-EGFR agent cetuximab in patients with gastric and gastroesophageal junction cancer. The primary of the EXPAND study was progression-free survival, assessed by an independent review committee. The study protocol was amended due to lower progression-free survival observed. Between June 2008 and December 2010, 904 patients from 25 countries were enrolled and randomised; 455 patients received capecitabine and cisplatin plus cetuximab and 449 received only capecitabine and cisplatin. Overall, patients were 74% male and 83% had stomach cancer; 97% of the patients had metastatic disease.

Patient outcome was similar between treatment groups and the primary and secondary endpoints were not met; progression-free survival was 4.4 versus 5.6 months and overall survival was 9.4 versus 10.7 months with cetuximab combination and control treatment, respectively. Overall response rates were 29% with cetuximab and 30% with control.

Safety profiles were consistent with those known for each agent but more grades 3/4 and serious adverse events were reported in the cetuximab arm. Negative results of this trial can not be explained by toxicity.

Tissue is available for biomarker analysis from 97% of included patients and the analysis is currently on-going. Dr. Arnaud Roth, who discussed the abstract during the Presidential session, questioned if this is the right setting to learn more on anti-EGFR inhibition in gastric cancer. In his opinion the EXPAND study represents a great opportunity for translational research and multivariate analyses testing; it is also an opportunity to establish sub-groups of gastric cancer by genomic expression profiling.

The advantage for such analyses is that the EXPAND was a large study in metastatic cancer, performed in homogeneous patient population; clinical database is of high quality, tumour material is already available and patients gave their consent for additional research. During the session he urged that academics get access to that material to help best scientific advances and to improve the outlook of gastric cancer patients.

In conclusion, no general benefit was seen from adding cetuximab to first-line capecitabine and cisplatin for treating patients with advanced gastric cancer and more study is needed to find effective treatments for these patients.