Case report: EGFR-mutant lung adenocarcinoma with the TP53 and RB1 mutations showed resistance to TKI therapy.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a standard treatment for patients with advanced non-small-cell lung cancer (NSCLC) harboring classic EGFR mutations. However, resistance to TKIs remains a major clinical challenge. The transformation from adenocarcinoma to small-cell lung cancer (SCLC) is a rare resistance mechanism to EGFR-TKIs. In this article, we report on 2 lung adenocarcinoma patients with EGFR mutations who developed EGFR-TKI resistance. In case one, the patient was initially diagnosed as lung adenocarcinoma with EGFR L858R, RB1 R445*, and TP53 Y205C mutations. EGFR-TKI failed to bring satisfactory curative effect with the emergence of EGFR T790M mutation and MET amplification and finally passed away. In case two, the patient was diagnosed with lung cancer harboring EGFR L747 and TP53 R342* mutations, and EGFR-TKIs brought a progression-free survival for nine months. However, EGFR-TKI resistance was acquired, and adenocarcinoma transformed into a complex of neuroendocrine carcinoma, SCLC, and lung adenocarcinoma, with the emergence of the EGFR L747, TP53 R342*, and RB1 mutations. Follow-up treatments failed to prevent tumor progression, and the patient died These 2 cases expand our understanding of EGFR-TKI resistance, SCLC transformation, and highlight the importance of histopathology and molecular characteristics for therapeutic strategies for transformed SCLC patients.