78IN - Is there a Role for Targeted Agents or Biologicals in Stage I–III NSCLC?

Abstract

ABSTRACT More than half of the patients with non-small cell lung cancer (NSCLC), including different tumor stages and histology subtypes, have actionable driver mutations. In patients with advanced NSCLC and activating EGFR mutations, randomized phase III trials with EGFR inhibitors (gefitinib, erlotinib and afatinib) demonstrated superior response rates and progression free survival compared with chemotherapy. Phase II trials showed high response rates for crizotinib in advanced NSCLC with ALK-translocation and the results of two randomized phase III trials are awaited. Preliminary data from phase I-II trials and retrospective series suggest further targets for tumor-specific therapies, including MET, ROS1, HER2, BRAF, KRAS, PI3K and others. Moreover, bevacizumab and cetuximab have shown clinical activity in phase III trials in combination with chemotherapy in patients with advanced NSCLC selected by histology and EGFR expression, respectively. Rapid molecular testing is now available at many institutions, and the translation of these novel therapies from stage IV to earlier stages has begun. Caution is warranted, because cure – not tumor response – is the ultimate goal of therapy, and the use of new drugs outside of a clinical trial in patients with stage I-III NSCLC may be risky. Of note, S0023 and BR.19 showed no benefit with the addition of gefitinib to a radical treatment in patients with localized NSCLC, irrespective of EGFR mutation status. Furthermore, phase III trials suggested a possible antagonism when EGFR-TKIs were combined with chemotherapy in patients with stage IV NSCLC. More recent studies indicate that such negative interaction may be avoided by pharmacodynamic separation (or intercalation), and that EGFR-TKIs as single agents could be used safely and effectively as induction therapy before surgery in carefully selected patients with stage I-III NSCLC. At the meeting, these data will be reviewed, and ongoing trials in this field will be discussed, including RADIANT (erlotinib), ADJUVANT (gefitinib), and ECOG 1505 (bevacizumab). Clinical cases will be presented to highlight problems and pitfalls of treating patients outside of controlled trials, and new avenues for clinical and translational research will be elucidated. Disclosure The author has declared no conflicts of interest.