Long-Term Efficacy of Immune Checkpoint Inhibitor for Squamous Cell Carcinoma Lesion Transformed From -Mutated Adenocarcinoma After Osimertinib Treatment: A Case Report.

Histologic transformation is one of the mechanisms of resistance to EGFR tyrosine kinase inhibitor in patients with NSCLC with mutation. The transformation from adenocarcinoma to squamous cell carcinoma (SCC) has been recently recognized as a mechanism of resistance to osimertinib. The prognosis after transformation to SCC is considered to be poor, and the therapeutic strategy for these patients is unclear. Herein, we report a case of long-term response to pembrolizumab monotherapy for an SCC-transformed lesion in a patient with -mutated adenocarcinoma after osimertinib treatment. A 68-year-old man underwent right upper lobectomy and was diagnosed with lung adenocarcinoma, pathologic stage IIA, with . Five years after the surgery, he was diagnosed with recurrence and administered osimertinib. Ten months after, biopsy for an enlarged subpleural lesion revealed SCC with , leading to a diagnosis of histologic transformation. Notably, the programmed death-ligand 1 expression level of the transformed lesion was higher than that of the adenocarcinoma (90% versus <1%). The size of the SCC lesion had reduced with pembrolizumab monotherapy, and the reduction was maintained for over 47 months since transformation. Nevertheless, the original adenocarcinoma lesion progressed after pembrolizumab therapy and was controlled by other cytotoxic drugs and readministration of osimertinib. Immune checkpoint inhibitor therapy is generally ineffective against -mutated adenocarcinoma. Nevertheless, it may be promising for achieving a good prognosis when -mutated adenocarcinoma transforms to SCC after developing EGFR tyrosine kinase inhibitor resistance-particularly if the transformed lesion has high programmed death-ligand 1 expression.