A randomized, double-blind phase 3 trial of adjuvant erlotinib (E) versus placebo (P) following complete tumor resection with or without adjuvant chemotherapy in patients (pts) with stage IB-IIIA EGFR positive (IHC/FISH) non-small cell lung cancer (NSCLC): RADIANT results.

7501 Background: The proven efficacy of E in advanced NSCLC warranted its evaluation in the adjuvant setting. BR.21 data suggested pts with EGFR positive tumors (IHC/FISH) were more likely to benefit from E. Methods: Completely resected IB-IIIA NSCLC pts were randomized 2:1 to receive E 150 mg qd or P for 2 years. Pts were stratified according to stage, histology, prior adjuvant chemotherapy, smoking status, EGFR FISH status, and country. The primary endpoint was disease free survival (DFS) in the full analysis set (FAS). Secondary endpoints included overall survival (OS) in the FAS and DFS and OS in the EGFR mutation (EGFR M+) subset (del19/L858R). Hierarchical testing procedure was used. Results: Between NOV 2007 and JUL 2010, 973 pts were randomized. Baseline characteristics were balanced between arms (age > 65 41%; female 41%; stage IB 51%, II 33%, IIIA 16% [AJCC 6th ed]; adenocarcinoma 59%; prior adjuvant chemotherapy 53%; never smoker 20%; Asian 17%; EGFR FISH+ 72% and EGFR M+ 16.5%). The planned number of events (410) for the final DFS analysis was reached in APR 2013; 277 (28%) pts had died. Median follow-up was 47 months (m). No statistically significant difference in DFS was observed in FAS; hierarchical testing rendered all secondary endpoints non-significant. The median treatment duration was 12 m for E and 22 m for P in FAS. Rash and diarrhea occurred in 58% and 52% pts for E vs 17% and 16% for P. Grade ≥3 rash and diarrhea occurred in 12.6% and 6.2% pts for E vs 0.3% and 0.3% for P. No drug-related adverse events led to death. Conclusions: Adjuvant E did not prolong DFS in the overall population. Further investigation in EGFR M+ pts is warranted. The safety profile of E was consistent with that in advanced disease. Clinical trial information: NCT00373425. Full analysis set. Median (m) HR (95% CI) P value E (N=623) P (N=350) DFS 50.5 48.2 0.90 (0.741-1.104) 0.3235 OS NR NR 1.13 (0.881-1.448) 0.3350 EGFR M+ subset Median (m) HR (95% CI) P value E (N=102) P (N=59) DFS 46.4 28.5 0.61 (0.384-0.981) 0.0391* OS NR NR 1.09 (0.545-2.161) 0.8153 Abbreviations: HR, hazard ratio; NR, not reached. *Not significant due to hierarchical testing.