Gefitinib as neoadjuvant therapy for resectable stage II-IIIA non-small cell lung cancer: a phase II study.

Abstract Introduction Currently, limited data on tyrosine kinase inhibitors as neoadjuvant therapy exists. This prospective study aimed to investigate the efficacy and safety of preoperative gefitinib in patients with stage II-IIIA operable NSCLC. Methods This was a single-arm, phase II trial performed in the Shanghai Cancer Center. Between August 2013 and October 2015, patients with operable stage II-IIIA NSCLC with epidermal growth factor receptor(EGFR) exon 19 deletion or exon 21 L858R mutation were enrolled. Patients were treated with preoperative gefitinib(250 mg once daily for 42 days), followed by surgical resection. The primary endpoint was objective response rate(ORR); secondary endpoints were the rate of major pathologic response(MPR), disease-free survival(DFS), overall survival(OS), and adverse events(AEs). ORR was defined as the proportion of patients achieving complete response or partial response radiologically. MPR was defined as no more than 10% viable tumor. Results Of the 35 eligible patients, 33 were considered as intention-to-treat population. ORR, the primary endpoint, was 54.5%(95% confidence interval [CI],37.7-70.7), and the rate of MPR was 24.2%(95% CI,11.9-40.4). Median DFS was 33.5 months(95% CI,19.7-47.3); median OS was not reached. Skin toxicity(24/35,68.6%) and gastrointestinal symptoms(17/35,48.6%) were the most common AEs; no patients reported grade 3 or 4 AEs. After surgery, four patients experienced chylothorax(4/33,12.1%). Patients with MPR had a prolonged survival compared with those without(DFS, p=0.019). Conclusions Neoadjuvant therapy with gefitinib in patients with stage II-IIIA NSCLC is safe and may be a viable treatment for patients whose tumors have EGFR mutations. Patients with MPR were associated with improved survival.