The different frequencies of histologic transformation after different EGFR-TKIs in EGFR-mutant adenocarcinomas

Abstract

Abstract Background The EGFR-mutant adenocarcinomas with histologic transformation usually had poor prognosis. However, few studies have focused on the different frequencies and molecular mechanism after the treatment of different tyrosine kinase inhibitors(TKIs). Methods Pathology was confirmed in 296 EGFR-mutant patients at baseline and recurrence. Among these patients, 190 patients were treated with gefitinib/erlotinib, 51 with afatinib and 55 with osimertinib. The sufficient tumor specimens from 9 patients were detected by next-generation sequencing. Demographics, disease features, and outcomes of these patients were analyzed. Results The frequencies of EGFR-mutant adenocarcinomas with histologic transformation after different EGFR-TKIs were quite different. The frequency of gefitinib/erlotinib group was 7.9% (15/190), while the others were 5.8% (3/51, afatinib group) and 14.5% (8/55, osimertinib group). The progression free survival (PFS) to different EGFR-TKIs were 10.7 months (gefitinib/erlotinib group), 9 months (afatinib group) and 7.7 months (osimertinib group), respectively. Four adenocarcinomas treated with gefitinib/erlotinib all harbored TP53 mutations at baseline. One adenocarcinoma after the treatment of afatinib had acquired MET amplification and transformed to small-cell lung cancer meanwhile. There were 2 patients treated with osimertinib transformed from adenocarcinomas to adenosquamous carcinoma and they were characterized by KRAS amplification and EGFR amplification. The others transformed to small-cell cancers were harboring with TP53, Rb1 and PIK3CA mutations. Conclusion The EGFR-mutant adenocarcinomas treated with osimertinib had the highest rate of histologic transformation. The genetic profiles vary greatly between transformation to squamous carcinomas and transformation to small-cell cancers in EGFR-mutant adenocarcinomas treated with osimertinib. Further verification is needed.