Long-term outcomes of neoadjuvant gefitinib in resectable stage II-IIIA non-small cell lung cancer: A phase II, prospective cohort study.

Background: Our previous study has showed the safety and efficacy of preoperative gefitinib in patients with stage II-IIIA resectable non-small cell lung cancer (NSCLC). This study aimed to report the long-term survival analysis and recurrent patterns.

Methods: This was a single-arm, phase II clinical trial. Patients with resectable stage II-IIIA NSCLC harboring EGFR exon 19 deletion or exon 21 L858R mutations were enrolled. Patients were administrated with preoperative gefitinib (250 mg once daily for 42 days), followed by surgical resection. The primary endpoint was objective response rate (ORR); secondary endpoints included the rate of major pathologic response (MPR), disease-free survival (DFS), overall survival (OS). MPR was defined as the presence of no more than 10 % viable tumor. Chi-square test was used to assess the differences in CNS recurrence rates and recurrent patterns.

Results: Of the 33 intention-to-treat patients, ORR 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). Among the investigated 28 patients, the median follow-up was 108.5 months. The median OS was 89.8 months (95 % CI, 44.37-NC), and the median DFS was 36.4 months (95 % CI, 18.9-NC). In addition, MPR continued to indicate significantly improved DFS, as well as OS (DFS, p = 0.015; OS, p = 0.037). The neoadjuvant gefitinib group showed prolonged DFS and OS than platinum doublet group (hazard ratio (HR) = 1.71, 95 % CI, 1.02-2.85, p = 0.038; and HR = 2.31; 95 % CI, 1.28-4.16, p = 0.0044, respectively). There was a significant difference in the distant recurrence patterns between the two groups (p = 0.032). Moreover, the gefitinib group showed similar overall brain metastasis rate than platinum doublet group (21.4 % versus 27.5 %).

Conclusions: With satisfying prognosis benefits and acceptable brain metastasis rate in long-term follow-up, gefitinib exhibited clinical viability for operable stage II-IIIA EGFR-mutant NSCLC over chemotherapy in the neoadjuvant setting. MPR was significantly associated with both prolonged DFS and OS, manifesting its potential as an essential endpoint for future neoadjuvant trials.