Retreatment With EGFR-Tyrosine Kinase Inhibitor After Disease Progression Following Gefitinib Induction and Chemoradiotherapy in EGFR-Mutant Stage III Non-small Lung Cancer: An Efficacy and Safety Analysis of the LOGIK0902/OLCSG0905 Study

Background and Objective:
In a prior phase II trial (LOGIK0902/OLCSG0905), we evaluated an eight-week induction of gefitinib followed by cisplatin-based chemoradiotherapy in patients with locally advanced, EGFR-mutated non-small cell lung cancer (NSCLC). While overall survival outcomes were favorable, over half of the patients experienced disease recurrence after completing the protocol therapy. This underscores the need to assess the clinical utility of retreating with EGFR-tyrosine kinase inhibitors (TKIs) in this setting. The current sub-analysis investigates the efficacy and safety of EGFR-TKI retreatment following disease progression.
Materials and Methods:
We analyzed 14 patients who experienced relapse after completing the protocol therapy and subsequently received any EGFR-TKI as post-progression treatment. The efficacy and safety of EGFR-TKI retreatment were evaluated in this cohort.
Results:
Of the 14 patients, 11 (78.6%) initially responded to gefitinib JBJ-09-063 during the protocol induction phase. Upon relapse, 9 patients (64.3%) were retreated with gefitinib, 3 (21.4%) with afatinib, and 2 (14.3%) with erlotinib monotherapy. The median duration of EGFR-TKI retreatment was 17.9 months (range: 0.7–45.5 months). The overall response rate (ORR) was 64.3% (9/14; 95% CI: 35.1%–87.2%), and the disease control rate was 85.7% (12/14; 95% CI: 57.2%–98.2%). Median progression-free survival (PFS) following EGFR-TKI retreatment was 11.8 months (95% CI: 5.7–20.7 months), and median overall survival was 47.4 months (95% CI: 31.8 months to not estimable). Reported adverse events were consistent with previously established safety profiles.
Conclusions:
Patients who relapsed after the initial gefitinib-based protocol demonstrated renewed sensitivity to EGFR-TKI retreatment, with durable responses and manageable toxicity. These findings support the clinical benefit of EGFR-TKI rechallenge in this setting.