Erbitux failed to meet both its primary endpoint of progression-free survival and secondary endpoint of overall survival in the first-line treatment of advanced non-small cell lung cancer in a Phase III trial. However, given that Erbitux’s efficacy was previously demonstrated in the larger Phase III FLEX trial, these latest results are unlikely to jeopardise a US approval for the same indication.

The FLEX trial, sponsored by ImClone System’s European marketing partner Merck Serono, randomized 1,125 patients with EGFR-detectable Stage IIIB/IV NSCLC to Erbitux plus cisplatin and vinorelbine versus chemotherapy alone. The overall survival was 11.3 months for patients treated with Erbitux, compared with 10.1 months for patients treated with chemotherapy only.

However, this survival improvement of 1.2 months in the FLEX trial came close to missing statistical significance, with a p-value of 0.044. Overall survival results of the BMS-099 trial, although not statistically significant, support those of the FLEX trial. Full results of the BMS-099 trial are expected later in 2008.

Currently, Avastin (bevacizumab; Genentech/Roche) is the only targeted therapy approved for the first-line treatment of advanced NSCLC. However, Erbitux will not necessarily compete with Avastin in this treatment setting.

The statistical power of the pivotal FLEX trial could generate delays in Erbitux’s approval if it prompts the FDA to request additional data. In addition to this, the failure of Erbitux to meet trial endpoints in the BMS-099 study may provide some barrier to uptake. However, in a market characterised by a high level of unmet need, the FLEX trial is ultimately likely to drive Erbitux’s approval for the first-line treatment of advanced NSCLC.

Related Research: Pipeline Insight: Non-Small Cell Lung Cancer