Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors Beyond Progressive Disease: A Retrospective Analysis for Japanese Patients with Activating EGFR Mutations

Introduction It is not determined whether the continuous use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) is reasonable for patients with activating EGFR mutations who have progressed with the drug. Methods We retrospectively analyzed the data from 2002 to 2010 of consecutive patients who had advanced non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations, and showed radiological disease progression after EGFR-TKI treatment as the first-line or second-line setting. We classified them into two groups: continuous EGFR-TKI and switching to chemotherapy, and comparedthe clinical outcome. Multivariate analysis for survival was carried out including age, gender, ECOG performance status (PS: 0-1/ 2-4), brain metastasis, EGFR mutations (deletions in exon 19 versus L858R), continuous EGFR-TKI (yes/no), initiation of EGFR-TKI (1st versus 2nd). Results A total of 551 NSCLC patients were screened for EGFR mutations in the period, and 210 patients had EGFR mutations. To explore the use of EGFR-TKI beyond progressive disease (PD), 46 patients were selected and analyzed. There were 9 males and 37 females, and median age was 65 years (42–86 years). Among them, 23 patients had deletions in exon 19, and 23 had a point mutation of L858R in exon 21. Twenty-five patients were continuing EGFR-TKI beyond PD. Twenty-one patients were switched to cytotoxic chemotherapy alone. The median overall survival (OS) was 60.8 months in the patients continuing EGFR-TKI, and 23.9 months in the patients receiving chemotherapy, presenting a significant difference between the two groups (P = 0.0081). Cox analysis showed that continuous EGFR-TKI after PD (HR 0.28, 95% CI: 0.10–0.76, P = 0.01) was associated with improved survival. Conclusion Continuous use of EGFR-TKI beyond PD may prolong OS compared with switching to cytotoxic chemotherapy in patients with activating EGFR mutations. A prospective study will be needed to confirm our results.