Metastatic collecting duct carcinoma is an aggressive form of RCC, which is poorly researched and understood. There is an unmet need for an effective treatment for these patients, and very few clinical trials allow these patients to take part.
This single centre, phase 2 trial tested cabozantinib in untreated patients with collecting duct carcinoma that had spread (metastatic). The study looked at survival outcomes and side effects to cabozantinib. The study also tried to identify DNA mutations that defined this subtype of RCC.
Twenty-five patients were enrolled in the study, of whom 23 were treated with cabozantinib. Most patients were male with an average age of 66. The most common sites of spread were the lymph nodes, lung, and liver. Patients were followed for an average of 8 months.
Thirty-five percent (35%) of patients responded to treatment and their cancer got smaller. There was one complete response to treatment and 7 partial responses. The average time to when the treatment stopped working and the cancer started growing again (progression-free survival) was 6 months.
All patients reported at least one mild to moderate side effect, the most common being fatigue, low thyroid gland activity (hypothyroidism), sore mouth, low appetite, hand-foot syndrome, high blood pressure and diarrhoea. Five patients reported serious side effects (2 blood clots, 2 high blood pressure, 1 fatigue), and there were no life-threatening side effects or deaths related to treatment. The cabozantinib dose was reduced in 17% of patients.
DNA sequencing was successful in 21 (91%) patients and there was no link between tumour mutations and response to cabozantinib. However, patients who responded well to treatment with more than 6 months progression-free survival had a high number of mutations affecting the breakdown of certain proteins in the tumour cells (deubiquitination), cell-cell communication, and a growth factor in the tumour cells.