Unusual EGFR mutation should influence advanced NSCLC treatment choice

Feb 25 2014

By Lynda Williams, Senior medwireNews Reporter

Non-small-cell lung cancer (NSCLC) patients with very unusual epidermal growth factor receptor (EGFR) mutations may be more likely to be benefit from first-line chemotherapy than a tyrosine kinase inhibitor (TKI), research suggests.

The post hoc analyses were performed for a study that compared the EGFR–TKI gefitinib 250 mg/day with paclitaxel 20 mg/m² plus carboplatin to an area under the curve of 6.0 on a 3-week cycle in advanced NSCLC patients with confirmed EGFR mutations, explain Hirohisa Yoshizawa (Niigata University Medical and Dental Hospital, Japan) and co-authors.

When data for seven patients with the rare G719X mutation and three with the unusual L861Q mutation were combined, the researchers found that these patients had significantly poorer overall survival (OS) than the 215 patients with the more common exon 19 deletion, the L858R mutation or both variants, at 12.0 versus 28.4 months.

When the 114 patients assigned to receive gefitinib were assessed separately, again patients with the unusual mutations had poorer OS than those with the more common variants, at 11.9 versus 29.3 months.

However, for the 113 patients assigned to receive paclitaxel plus carboplatin, there was no significant difference in the OS of patients with rare and more common EGFR mutations, at 22.8 and 28.0 months, respectively.

A similar pattern was also found for progression-free survival, Yoshizawa et al report in the Journal of Thoracic Oncology.

“Our results are consistent with other clinical studies on EGFR-TKIs in patients with uncommon EGFR mutations,” the team comments.

Noting that some patients with common EGFR mutations do respond well to TKI therapy, the researchers recommend gefitinib be considered for patients with disease progression after first-line chemotherapy.

Ongoing trials are also investigating the efficacy of combined gefitinib and carboplatin plus pemetrexed compared with gefitinib alone for patients with both the common and rare EGFR mutations, they add.

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