First-generation EGFR tyrosine kinase inhibitor therapy in 106 patients with compound EGFR -mutated lung cancer: a single institution’s clinical practice experience

摘要

Background The antitumour efficacy of tyrosine kinase inhibitors (TKIs) in lung cancer patients with compound epidermal growth factor receptor ( EGFR ) mutations has not been resolved. Our study summarizes a single institutional experience of first-generation TKI therapy for lung cancers with compound EGFR mutations. Methods A total of 106 consecutive patients with tumours bearing compound EGFR mutations were identified between January 2012 and May 2016; all patients received first-generation TKI therapy. Deletions in exon 19 and the L858R point mutation in exon 21 were considered common mutations; T790M was considered separately because of its association with TKIs resistances. Any other mutation was defined as a rare mutation. Patients were divided as follows: double common mutations (group A); common plus T790M mutations (group B); common plus rare mutations (group C); double rare mutations (group D); and rare plus T790M mutations (group E). A separate group of 115 consecutive patients with a single common mutation was created for comparative analysis (group F). Results The frequency of patients with compound EGFR was 2.9% (114/3925) and their response rate to first-generation TKIs was 50.9%, which was not significantly different from group F (67.0%, P =?0.088). The progression-free survival (PFS) of the 106 patients receiving TKI therapy was worse than that of group F (median, 9.1 vs. 13.0?months, respectively; P ?0.001). The PFS of the compound mutation group was shorter than that of the single common mutation group (median, 10.1?months in group A, P =?0.240; 9.1?months in group B, P ?0.001; 9.6?months in group C, P =?0.010; 6.5?months in group D, P =?0.048; 5.4?months in group E, P =?0.017). Patients with a co-occurring mutation in exon 20 (excluding T790M) exhibited significantly worse PFS than the patients with other compound mutations or with a single common mutation (median, 6.5 vs. 9.1 vs. 13.0?months, respectively, P =?0.002). Conclusions There was significant heterogeneity among the compound EGFR mutations and their response to first-generation TKIs. Individualized treatment in clinical practice should be considered for each case.