A gene called MET codes for a protein called MET tyrosine protein kinase (also called hepatocyte growth factor receptor), which stimulates the growth and development of tumours. MET tyrosine protein kinase is a key driver of the growth and development of papillary renal cell carcinoma (pRCC). In this study presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) over the weekend, various MET tyrosine protein kinase inhibitors cabozantinib, crizotinib, and savolitinib were compared to standard care with sunitinib for the treatment of patients with papillary RCC.
One hundred and fifty-two (152) patients with metastatic papillary RCC who had received up to one previous therapy (excluding vascular endothelial growth factor (VEGF) and MET inhibitors) were randomly allocated to one of four treatment groups to receive either sunitinib, cabozantinib, crizotinib, or savolitinib.
Five patients were excluded from the analyses, and randomisation to the savolitinib (29 patients) and crizotinib (28 patients) groups was stopped early, but completed for both the sunitinib (46 patients) and cabozantinib (44 patients) groups. The time to when the drug stops working and the cancer starts growing again (progression-free survival) was significantly longer in patients in the cabozantinib group (9 months) than in patients receiving sunitinib (5·6 months). Tumour shrinkage (response rate) for cabozantinib was 23% versus 4% for sunitinib. Savolitinib and crizotinib did not improve progression-free survival compared with sunitinib. Severe or life-threatening side effects were reported by 69% of patients on sunitinib, 74% on cabozantinib, 37% on crizotinib, and 39% of patients taking savolitinib. There was one death due to a blood clot (thromboembolism) in the cabozantinib group.
In summary, cabozantinib significantly extended progression-free survival in patients with previously-treated, metastatic papillary RCC compared with standard treatment with sunitinib.