Abstract Introduction Targeted therapy plays a crucial role in the management of non-small cell lung cancer (NSCLC). Selpercatinib, a selective RET kinase inhibitor, is approved for patients with metastatic NSCLC harboring RET gene fusions. Although generally well tolerated, selpercatinib has been associated with rare cases of chylous ascites and pleural effusions. We describe a case with this rare adverse event. Case A 70-year-old man presented with a right middle lobe lung mass identified on imaging (Figure 1). Staging endobronchial ultrasound-guided biopsy confirmed adenocarcinoma, with molecular profiling revealing an RET fusion. He was initiated on selpercatinib. Although overall he tolerated therapy well, he developed hypertension and gastrointestinal symptoms responsive to medications. Several months later, surveillance imaging demonstrated radiographic response in the primary lung mass without evidence of disease progression yet incidentally revealed a right pleural effusion. Diagnostic thoracentesis yielded 900 mL of milky white fluid, and pleural fluid analysis showed LDH 274 U/L, total protein 1.2 g/dL, glucose 50 mg/dL, cholesterol 473 mg/dL, and triglycerides 3,965 mg/dL consistent with a chylothorax. Cytology and flow cytometry were negative for malignancy. Given disease response, patient and family were reluctant to stop selpercatinib. Conservative management with a low-fat diet and octreotide was initiated, resulting in stable effusion size on follow-up imaging, without disease progression or significant symptoms. Discussion Chylothorax can arise from traumatic or non-traumatic etiologies. It is commonly observed in the setting of malignancy, most frequently with lymphomatous tumors. Rarely, it can occur if malignant disease involves or compresses the thoracic duct. Chylous effusions are a rare but known side effect of RET tyrosine kinase inhibitors, and there is a very low incidence reported. Management may be challenging especially when there is a positive response to this targeted therapy. Our case demonstrates that recognized selpercatinib-induced chylothorax can be managed conservatively with dietary modifications and somatostatin analogs like octreotide, thus allowing continuation of effective targeted therapy while avoiding more invasive interventions. Physicians should be aware of this potential adverse effect, thus allowing appropriate management and avoidance of unnecessary diagnostic procedures or therapeutic interventions. This abstract is funded by: None
Khoury et al. (Fri,) studied this question.