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Hyperprogressive disease (HPD) is a paradoxical phenomenon involving the acceleration of tumor progression after treatment with immune checkpoint inhibitors (ICIs). A 66-year-old male smoker with advanced lung adenocarcinoma started pembrolizumab for progressive disease following first-line chemotherapy. He developed HPD after two cycles, and a re-biopsy revealed transformation to small-cell carcinoma. He subsequently underwent two lines of chemotherapy for small-cell carcinoma until progression and ultimately died. Transformation to small-cell carcinoma may be a cause of HPD during ICI therapy. The possibility of pathological transformation should be considered in cases of HPD with resistance to ICI therapy.

Hyperprogressive Disease in Lung Cancer with Transformation of Adenocarcinoma to Small-cell Carcinoma during Pembrolizumab Therapy