Efficacy and safety of tarlatamab, a DLL3-targeted bispecific T-cell engager, in a patient with advanced esophageal small-cell neuroendocrine carcinoma: a case report

The limited efficacy of current therapeutic options highlights a clear unmet need in patients with digestive neuroendocrine carcinoma. Tarlatamab is a bispecific T-cell engager targeting CD3 on T cells and delta-like ligand 3 on tumor cells. Since delta-like ligand 3 is highly expressed in digestive neuroendocrine carcinomas, tarlatamab might be a potential treatment option in this setting. However, the efficacy of tarlatamab in patients with digestive neuroendocrine carcinoma remains unknown. Herein, we report a case of metastatic esophageal neuroendocrine carcinoma that achieved a complete radiologic response following treatment with tarlatamab. A 47-year-old woman presented with progressive dysphagia and was diagnosed with esophageal small-cell neuroendocrine carcinoma with mediastinal lymph node metastases. She received first-line chemoimmunotherapy and radiotherapy to the primary tumor and mediastinal lymph nodes. Following three months of maintenance therapy with atezolizumab, new metastatic lesions in the liver and brain developed. Second-line treatment with tarlatamab was initiated. Tarlatamab induced complete resolution of the metastatic lesions in the liver and brain, without adverse events attributable to tarlatamab. This case underscores the potential value of delta-like ligand 3-targeted therapy with tarlatamab in metastatic digestive neuroendocrine carcinoma, a rare and highly aggressive malignancy with few effective treatment options.