Maintained Sensitivity to EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Lung Cancer Recurring after Adjuvant Erlotinib or Gefitinib

Abstract

Given the unprecedented efficacy of EGFR tyrosine kinase inhibitors (TKI) in advanced EGFR-mutant lung cancer, adjuvant TKI therapy is an appealing strategy. However, there are conflicting findings regarding the potential benefit of adjuvant EGFR-TKI in patients with lung cancer harboring EGFR mutations. To better understand these results, we studied the natural history of lung cancers which recurred despite adjuvant TKI. Patients with recurrent EGFR-mutant lung cancer following adjuvant TKI were identified using an Institutional Review Board-approved mechanism. Recurrent cancer specimens were tested for resistance mutations. Sensitivity to retreatment with EGFR-TKI was evaluated. Twenty-two patients with cancers harboring an EGFR sensitizing mutation received adjuvant erlotinib or gefitinib for a median of 17 months (range 1-37 months). T790M was more common in cancers which recurred while receiving TKI than in those which recurred after stopping TKI (67% vs. 0%, P = 0.011). Fourteen patients who developed recurrence after stopping EGFR-TKI were retreated, with a median time to progression of 10 months and radiographic response seen in 8 of 11 patients with evaluable disease (73%). Recurrence of EGFR-mutant lung cancer after stopping adjuvant TKI should not preclude a trial of TKI retreatment; a phase II trial of erlotinib in this setting is underway. Studies of adjuvant EGFR-TKI will underestimate the potential survival benefit of adjuvant TKI for patients with EGFR-mutant lung cancers if retreatment at recurrence is not given.