Continuation of gefitinib beyond progression in patients with EGFR mutation-positive non-small-cell lung cancer: A phase II single-arm trial

Objectives: Several studies have demonstrated the promise of continuation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) beyond progression in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). The aim of the present study is to clarify the efficacy of continuation of gefitinib in patients with NSCLC beyond progression. Materials and methods: A total of 50 patients with EGFR-mutant NSCLC who progressed based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria during gefitinib treatment were eligible. The primary endpoint was progression-free survival-2 (PFS2; time from first gefitinib dose to off-gefitinib progression). Secondary endpoints were PFS1 (time from first gefitinib dose to RECIST 1.1 progression); the difference between PFS2 and PFS1 (PFS2-PFS1); overall survival (OS); and safety. Patients received gefitinib 250 mg/d orally until symptomatic progression or at the investigator's discretion. Results: Between January 2016 and March 2017, 50 patients were enrolled in this study. One patient withdrew consent, leaving a total of 49 patients to be evaluated. The median PFS2-PFS1 was 5.1 months (95% CI, 2.5-7.8), and the median PFS2 was 27.7 months (95% CI, 21.6-33.9). Twelve patients (24.4%) continued gefitinib therapy for 14 months (median value, range 7.2-20.3 months) after RECIST 1.1 progression. The median OS was not reached. Patients were classified by the characteristics of progression at the time of enrollment. PFS2-PFS1 was significantly shorter in patients with pleural metastasis or pleural effusion compared with the other types of progression (1.8 months vs. 7.1 months, p-value = 0.005). Conclusion: In patients with EGFR-mutant NSCLC who experience progression, it is beneficial to maintain gefitinib treatment with local treatment such as radiotherapy until symptomatic progression. However, in patients with pleural metastasis or effusion, continuation of gefitinib beyond progression should be carefully determined on a case by case basis.