Third-generation tyrosine kinase inhibitor in the treatment of epidermal growth factor receptor mutated squamous cell lung cancer: a tailored therapy approach.

We reported the case of a male patient suffering from a metastatic squamous cell carcinoma, harboring a complex inframe deletion in exon 19 of epidermal growth factor receptor (EGFR), treated with erlotinib and osimertinib and subsequently with immunotherapy. A 54-year-old male, with a light smoking history, presented in October 2015 with metastatic squamous cell lung cancer (SqCLC). Deletion p.E746_S752>V in EGFR exon 19 was found and after progression to erlotinib treatment, the liquid biopsy-based re-assessment highlighted a p.T790M EGFR mutation. Osimertinib was then started. After 5 cycles disease progression was detected and nivolumab was started. A subsequent clinical and radiological progression occurred after 3 nivolumab administrations. Next-generation sequencing (NGS) analysis, performed on metastatic tissue, confirmed the original EGFR deletion and showed also the presence of EGFR p.G724S and TP53 p.P152L mutations. Patient died in December 2017. The reported case highlighted tumor's molecular features prominent role over histology, offering further insights about druggable mutations in SqCLC. Furthermore, we confirm the emerging role of EGFR p.G724S mutation as a Osimertinib resistence mechanism.