Durable clinical response to immunotherapy in EGFR-mutated lung adenocarcinoma with squamous cell carcinoma transformation and high expression of PD-L1 after resistance development: A case report

Histological transformation is one of the mechanisms of resistance to targeted therapy, chemotherapy and immunotherapy in non-small cell lung cancer (NSCLC). The histological transformation from adenocarcinoma (ADC) to squamous cell carcinoma (SCC) after tyrosine kinase inhibitor (TKI) treatment is rare in epidermal growth factor receptor (EGFR)-mutated NSCLC. However, few effective strategies have been previously reported for these patients. Here, we report a lung ADC patient with EGFR 19del who showed a poor response to EGFR-TKI therapy and acquired histological transformation to SCC with high expression of programmed cell death-ligand 1 (PD-L1) after developing EGFR-TKI resistance and undergoing sequential radiotherapy and chemotherapy. The patient then received combination treatment with the immune checkpoint inhibitor (ICI) sintilimab plus anlotinib followed by sintilimab maintenance therapy, which achieved long-term survival. This case report discusses the potential mechanisms of SCC transformation in EGFR-mutated NSCLC and speculates that immunotherapy plus anti-angiogenic therapy may be a good choice for EGFR-mutated lung ADC patients with SCC transformation and high expression of PD-L1 after TKI resistance development.