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.
Keywords: Compound mutations; EGFR; TKIs.