Hirsch FR et al. (2008) Fluoresence in situ hybridization subgroup analysis of TRIBUTE, a phase III trial of erlotinib plus carboplatin and paclitaxel in non-small cell lung cancer. Clin Cancer Res 14: 6317–6323

In 2005, the TRIBUTE trial demonstrated that addition of erlotinib to chemotherapy did not improve overall survival or time to progression in patients with advanced non-small-cell lung cancer (NSCLC). On the basis that increased EGFR copy number is associated with improved overall survival and time to progression after treatment with anti-EGFR agents, Hirsch et al. examined whether EGFR copy numbers could predict outcome in patients with NSCLC.

Fluorescent in situ hybridization was used to assess EGFR gene amplification (i.e. increased copy numbers) in 275 tumor samples obtained from TRIBUTE participants. Of these samples, 100 showed amplification of EGFR and 145 did not (EGFR+ and EGFR−, respectively). For patients whose tumors were EGFR+, the median time to progression rates were 6.3 months and 5.8 months for patients who received chemotherapy plus erlotinib, and for those who received chemotherapy plus placebo (P = 0.0430). The median times to progression for EGFR− patients were 4.6 months and 6.0 months for these groups, respectively (P = 0.0895). The objective response rate in patients whose tumors were EGFR+ and who received erlotinib was particularly pronounced after completion of chemotherapy, which suggests that erlotinib could offer benefits as maintenance therapy. No significant effect of erlotinib on the objective response rate was seen in EGFR− patients.

Although EGFR amplification does not correlate with improved survival, these results suggest that erlotinib prolongs time to progression in patients with NSCLC whose tumors show increased copy numbers of EGFR.