• No overall disease-free survival (DFS) advantage was observed with adjuvant erlotinib in patients (n = 973) with early-stage resected EGFR-expressing NSCLC.
• In the subset of patients with EGFR del(19) and L858R mutations ​
(n = 161), DFS favored adjuvant erlotinib, although this was not statistically significant.

Dr Spigel points out that this important adjuvant study of erlotinib was launched in 2006, when the significance of EGFR tumor mutations was recently beginning to be appreciated, and, as such, a majority of the patients enrolled had EGFR wild-type disease. Therefore, the overall conclusion showing a lack of benefit was predictable, and although the subset analysis of the EGFR mutation-positive subgroup demonstrated a reduction in risk of relapse with adjuvant erlotinib (DFS HR = 0.61), it did not meet the strict criteria for statistical significance for an unplanned analysis.

One of the complicating factors of these data — in addition to the fact that the EGFR mutation-positive subset consisted of only 161 patients — is that more than a quarter of those receiving adjuvant erlotinib had treatment discontinued because of adverse events. It could be that the third-generation EGFR TKIs will demonstrate a greater adjuvant benefit, not only because of improved efficacy but also because better tolerability will allow patients to receive treatment longer and without interruption. Dr Spigel and many investigators attempt to place eligible patients on ongoing adjuvant trials but do not use EGFR TKIs as adjuvant treatment outside of a research setting.