Papillary kidney cancer is a rare subtype of renal cell carcinoma (RCC), and is characterised by changes in a gene called MET. The CREATE study from the European Organisation for the Research and Treatment of Cancer (EORTC) investigated crizotinib in patients with type 1 papillary RCC. Twenty-three (23) patients were treated, only 4 of which were MET-positive. Of these MET-positive patients, the response rate was 50% and one patient had stable disease. Three patients survived for 1 year without progression of their disease. A partial response was also seen in one of the MET-negative patients (16 patients) lasting more than 9.9 months, and 1-year overall survival rate was 72%, while in the 3 patients with unknown MET status, 1-year overall survival rate was 100% and one patient had a partial response lasting more than 6.9 months.
However, most patients did not respond to the drug, and it appears that crizotinib has selective activity in those patients who are MET-positive. It also remains to be seen whether crizotinib benefits patients with type 2 papillary kidney cancer, which is more common than type 1.
In summary, crizotinib is active and well tolerated in advanced, metastatic type 1 papillary RCC achieving objective responses and long-lasting disease control in MET-positive patients. Durable responses are also seen in MET-negative patients and patients with unknown MET status, suggesting the presence of other alterations of MET or alternative pathways.