Efficacy and Safety of Gefitinib as Third-line Treatment in NSCLC Patients With Activating EGFR Mutations Treated With First-line Gefitinib Followed by Second-line Chemotherapy: A Single-Arm, Prospective, Multicenter Phase II Study (RE-CHALLENGE, CTONG1304)

OBJECTIVE: There is no standard care for advanced non–small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation in the third line. Our study aimed to assess the efficacy and safety of gefitinib as a third-line re-challenge treatment for advanced NSCLC patients with EGFR mutation. MATERIALS AND METHODS: It was a multicenter, open-label, single-arm, phase II study. Stage IIIB/IV NSCLC patients with EGFR exon 19del/L858R mutation, who had benefited from first-line gefitinib treatment followed by second-line chemotherapy, received gefitinib 250 mg/d. The primary objective was disease control rate (DCR) at week 8. RESULTS: Predefined DCR was achieved in 69.8% (95% confidence interval, 49.87-74.91) patients and objective response rate was reported in 4.7% (95% confidence interval, 0.78-13.06) patients. Median progression-free survival (PFS) was 4.4 months and overall survival (OS) was 10.3 months. Baseline T790M-negative patients achieved favorable DCR compared with T790M-positive patients (78.1% vs. 45.5%, P=0.0418), significantly longer median PFS (4.7 vs. 2.0 mo, P=0.0009) and median OS (15.2 vs. 7.7 mo, P=0.0132). We observed a negative correlation of PFS (r=−0.4396, P=0.0032), and OS (r=−0.3630, P=0.0167) with mutation abundance of exon 19del/L858R at baseline. CONCLUSIONS: Re-challenge with gefitinib is effective and could be a choice for third-line patients after the first-line EGFR-TKI treatment and second-line chemotherapy, especially for the T790M-negative patients.