MET Inhibitors for Papillary Renal Cell Carcinoma

BACKGROUND: Papillary renal cell carcinoma (PRCC) has a relatively poor prognosis in the metastatic setting. In contrast to clear cell kidney cancer, there are limited treatment options specifically tested in PRCC. Alterations in the MET pathway are common in PRCC and may play a pivotal role in promoting tumor growth and the development of resistance to systemic therapy. OBJECTIVE: Current data on the efficacy of MET inhibitors over standard of care in PRCC is immature and evolving. The purpose of this systematic review is to assess and summarize the results and limitations of landmark trials of MET inhibitors for PRCC as well as to discuss barriers faced by trials of these drugs. METHODS: Manuscripts and abstracts were collected from PubMed, the American Society of Clinical Oncology (ASCO) historical abstracts and European Society for Medical Oncology (ESMO) historical abstracts. Included studies must have been either a clinical trial, systematic review or narrative review and included PRCC patients. Patients must have been treated with a selective or non-selective MET inhibitor. After the final application of criteria, 30 studies were included. RESULTS/CONCLUSIONS: Cabozantinib has the best evidence for use showing improved outcomes in PRCC. Other MET inhibitors, including savolitinib, crizotinib, and foretinib have shown possible benefit in patients with MET-positive disease, but the inconsistent definition of MET status and a low patient accrual rate prevented further extrapolation of the individual trial results. Future trials of single agent savolitinib, as well as combination MET inhibitor/ immuno-oncology (IO) therapies, have the potential to change the therapeutic landscape of using MET inhibitors for PRCC.