Tyrosine kinase inhibitors (TKIs) in advanced NSCLC increase progression-free survival (PFS), but in general do not change overall survival (OS).a In a randomized, double-blind phase 3 trial (RADIANT), the safety and efficacy of the tyrosine kinase inhibitor (TKI) erlotinib (E) was explored in the adjuvant setting;b now, O’Brien and colleaguesc presented the final follow-up from RADIANT. In this study, completely resected IB–IIIA NSCLC patients were randomized 2:1 to receive E 150 mg daily or placebo (P) for 2 years. The primary endpoint was disease-free survival (DFS) in the full analysis set (FAS). Secondary endpoints included OS in the FAS and DFS and OS in an EGFR mutation (M+) subset (del19/L858R). A total of 973 patients were randomized and the planned final analysis was performed and reported after 410 DFS events.d
In the current presentation, the median follow-up was 59.6 months (95% CI 56.7–61.2). There was no statistically significant difference in DFS or OS overall or in the EGFR M+ group. The OS data remain immature with 33.5% deaths in the E arm and 31.4% in the P arm. The most common sites of relapse (>15% patients) overall and in EGFR M+ patients were the lungs and brain in E-treated patients, and the lungs, bone, and brain in P patients. Among the 13 patients in the EGFRM+ subgroup with brain as the site of relapse, 11 relapsed after E cessation. There were no new safety concerns compared to previous reports. The authors concluded that overall, adjuvant E did not prolong DFS; a trend for E benefit previously observedd in the EGFR M+ subgroup was no longer apparent in this analysis. EGFR mutation status was not a stratification factor in this trial and was not a prognostic factor. Further results from ongoing trials are awaited to determine the role of TKIs as adjuvant therapy in EGFR M+ early-stage lung cancer, but based on these data, E following resection of adjuvant chemotherapy did not prolong DFS in patients with EGFR-expressing tumors.
