A prospective phase II study of induction erlotinib therapy in stage IIIA-N2 non-small cell lung cancer.

7039 Background: Stage IIIA NSCLC represents a heterogeneous group of patients with ipsilateral mediastinal (N2) lymph nodes involvement. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide dramatic responses in patients with non-small cell lung cancer (NSCLC) carrying EGFR mutations. The purpose of this study is to evaluate the role of induction EGFR-TKI therapy in IIIA-N2 NSCLC. Methods: Patients with resectable NSCLC of stage IIIA-N2 were assigned to either induction erlotinib arm or induction gemcitabine/carboplatin(GC) arm based on the EGFR mutations analysis (NCT00600587) . Study Design: Phase II, factorial Assignment, Safety/Efficacy; Primary outcome measures: Response to Induction Therapy; Estimated enrollment: 5 cases with partial response in the erlotinib arm. Results: From January 2008 till June 2011, 24 patients with IIIA-N2 NSCLC diagnosed by mediastinoscopy or PET/CT have been enrolled. Twelve cases with EGFR mutation were assigned to the erlotinib arm (30-42 days), while 12 cases harboring wild-type EGFR received the GC regimen (3 cycles). The primary end point of the response rates were 58% (7/12) for the erlotinib arm and 33% (4/12) for the GC arm (P=0.49). The pathological N2 complete response rates were 17% for the erlotinib arm and 25% for the GC arm (P=0.64). In the erlotinib arm, the most common failure model after initial therapy was distant metastases (9/10), especially brain metastases (3/9). The median progression free survival time was 7 months for the erlotinib arm and 9 months for the GC arm (P=0.27). The median overall survival was 27 months for the erlotinib arm and 23 months for the GC arm (P=0.52). In addition, four cases in the erlotinib arm got partial response to the 2nd EGFR-TKI therapy after progression to erlotinib induction therapy and the following thoracotomy. Conclusions: Induction erlotinib therapy in IIIA-N2 NSCLC with EGFR activating mutation is a promising strategy. Distance metastases were major failure model. A multicenter, randomized, phase II study evaluating efficacy and safety of erlotinib vs GC as neoadjuvant therapy for stage IIIA-N2 NSCLC patients with EGFR mutations (NCT01407822) is currently recruiting participants.