Cabozantinib-related pneumothorax in rapidly responding pts
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The present case series has been reported in THE LANCET, Oncology.

A 71-year-old man with renal cell carcinoma with symptomatic bilateral lung metastases and multiple subpleural lesions started second-line cabozantinib (60 mg orally daily) after disease progression on pazopanib. After 3 months of therapy, the patient presented at the emergency department and complained of a worsening of his dyspnoea, leading the authors to suppose that disease progression had occurred.

However, a CT scan revealed an impressive volumetric reduction of the lung nodules but the onset of an apical grade 3 left pneumothorax. The patient was treated with thorax drainage with complete pneumothorax resolution and no further sequelae. Given this excellent response, cabozantinib treatment was continued. So far, the patient remains on cabozantinib treatment, with a treatment duration of 5 months.

The second case of pneumothorax was observed in a 69-year-old woman with metastatic renal cell carcinoma 1 month after beginning second-line cabozantinib at a dose of 60 mg daily. The patient had one subpleural lung lesion 5 cm in size.

The patient presented at the emergency department with a sudden worsening of dyspnoea, which led to a diagnosis of grade 3 pneumothorax and treatment with drainage of the pneumothorax, which was ipsilateral to the pulmonary metastasis. Treatment with cabozantinib was continued, with a partial response recorded at subsequent disease evaluations.

Key takeaways:-
- Tumour necrosis—as a result of a rapid, dramatic response to cabozantinib—of subpleural lung metastases might explain the pathogenesis of the pneumothorax in both these cases.

- Cabozantinib is the only approved tyrosine kinase inhibitor that has been shown to increase overall survival, progression-free survival, and overall responses compared with everolimus in previously treated patients with metastatic renal cell carcinoma.

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