A Prospective Phase II Study of Induction Erlotinib Therapy in Stage IIIA-N2 Non-Small-Cell Lung Cancer

ABSTRACT 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 was 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 gemcitabine/carboplatin(GC) arm based on the EGFR mutations analysis (NCT00600587). Study design Factorial Assignment, non-randomized, safety/efficacy; primary outcome measures: response to induction therapy. 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 (three cycles). The most common side-effects in the erlotinib arm were rash (90%) and diarrhea (40%). The primary end point of the response rates were 58% (7 of 12) for the erlotinib arm and 33% (4 of 12) for the GC arm (P = 0.49). The pathological N2 complete response rates were 16.7% for the erlotinib arm and 25% for the GC arm (P = 0.64). In the erlotinib arm, the most common failure model was distant metastases (9 of 10), especially brain metastases (3 of 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 27.3 months for the erlotinib arm and 23.2 months for the GC arm (P = 0.52). In addition, four cases in the erlotinib arm got partial response to the second EGFR-TKI therapy after progression to erlotinib induction therapy and the following thoractomy. 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 versus GC as neoadjuvant therapy for stage IIIA-N2 NSCLC patients with EGFR activating mutations (NCT01407822) is currently recruiting participants.