Significant benefits of osimertinib in treating acquired resistance to first-generation EGFR-TKIs in lung squamous cell cancer: A case report.

BACKGROUND

Lung squamous cell cancer (LSCC) rarely harbors epidermal growth factor receptor (EGFR) mutations, even much rarer for acquired T790M mutation. Although clinical trials of AURA series illustrated that non-small cell lung cancer (NSCLC) with EGFR T790M mutation can benefit from osimertinib, only five LSCC patients were enrolled in total; moreover, the efficacy for LSCC was not shown in the results. Therefore, the response of LSCC to osimertinib is still unclear to date.

CASE SUMMARY: We report an LSCC case with T790M-related acquired resistance after treatments with first-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and benefited from osimertinib significantly. A 63-year-old Chinese man was diagnosed with stage IV (cT2N2M1b) LSCC harboring an EGFR exon 19-deletion mutation. Following disease progression after gefitinib and multi-line chemotherapy, re-biopsy was conducted. Molecular testing of EGFR by amplification refractory mutation system-polymerase chain reaction detected the exon 19-deletion without T790M mutation. Therefore, the patient was given erlotinib, but progression developed only 3 mo later. Then the frozen re-biopsy tissue was tested by next-generation sequencing (NGS), which detected an EGFR T790M mutation. However, he was very weak with symptoms of dysphagia and cachexia. Fortunately, osimertinib was started, leading to alleviation from the symptoms. Four months later, normal deglutition was restored and partial response was achieved. Finally, the patient achieved an overall survival time period of 29 mo.

CONCLUSION

Our findings highlight that EGFR T790M mutation may also be an important acquired drug resistance mechanism for LSCC and offer direct evidence of the efficacy of osimertinib in LSCC with T790M mutation. NGS and better preservation conditions may contribute to higher sensitivity of EGFR T790M detection.