TOPICAL: Randomized phase III trial of erlotinib compared with placebo in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC) and unsuitable for first-line chemotherapy.

7504 Background: Poor performance status (PS) NSCLC is an important, under-studied group of lung cancer patients, affecting 30-40% of patients. We determined the role of erlotinib plus best supportive care (BSC) in chemo-naïve, poor PS advanced NSCLC patients. Methods: Chemo-naïve NSCLC patients (ECOG PS 2/3 or PS 0/1 unfit for platinum chemotherapy; stage IIIB/IV) were randomized to erlotinib (150 mg/d) plus BSC (n = 350) or placebo plus BSC (n = 320). Endpoints were overall survival (OS), progression-free survival (PFS), response rate, and toxicity. The trial had 90% power to detect an increase in 1-year OS from 10% to 17.5%. Results: Between 2005 and 2009, 670 patients were randomised to either erlotinib (350) or placebo (320), from 78 UK centres. Median age was 77 yrs (range 42-91); 61% male; 38% adenocarcinoma, 39% squamous histology; the % with ECOG PS score of 0/1, 2 and 3 were 16%, 55% and 29% respectively; 35% stage IIIB and 65% stage IV disease. Baseline patient characteristics were balanced between the groups. At the time of analysis, 559 patients had died. Hazard ratio (HR; erlotinib vs placebo) for OS was 0.98 95% CI 0.82-1.15; p = 0.77. PFS HR was 0.86 0.74-1.01, p = 0.07. Pre-specified subgroup analyses showed significant longer OS and PFS for females only: HR of 0.75 0.57-0.99, p = 0.04 and 0.64 0.49-0.83, p = < 0.001 respectively. PFS HR for adenocarcinoma was 0.74 0.57-0.97, p = 0.03. PFS HR according to gender and histology were: 0.68 0.46-0.99, p = 0.046 females with adenocarcinoma; 0.62 0.43-0.89, p = 0.01 females with non-adenocarcinoma; 0.85 0.59-1.22, p=0.37 males with adenocarcinoma; and 1.14 0.89-1.45, p = 0.31 male with non- adenocarcinoma. As expected, increased Grade 3/4 rash and diarrhoea were observed in patients receiving erlotinib. Conclusions: Overall, erlotinib plus BSC did not improve OS, but there was some evidence of benefit for PFS. However, there was a clear effect on both OS and PFS for females, and PFS for adenocarcinoma. However, the effect in adenocarcinoma was largely driven by female patients. Final analyses, including EGFR mutation, VeriStrat serum tests and QoL will be presented. No significant financial relationships to disclose.