Are tyrosine kinase inhibitors fit for purpose in the treatment of metastatic papillary renal cell carcinoma?

Abstract

Renal cell carcinoma encompasses a range of histological subtypes. The treatment of metastatic disease in this context remains challenging. Papillary renal cell carcinoma is the second most common subtype and forms a significant subsection of non-clear cell renal cell carcinoma. Tyrosine kinase inhibitors form a significant part of the treatment of this largely incurable disease; however, outcomes tend to be poor. The aim of this article is to scrutinise whether these treatments are evidence-based in their use for metastatic papillary renal cell carcinoma and if good outcomes are reported. A literature review was made using PubMed of major prospective and retrospective studies. The European Association of Urology and European Society of Medical Oncology have both published guidance suggesting sunitinib should be offered first line in the treatment of metastatic papillary renal cell carcinoma. This, however, is based upon weak evidence produced by the ASPEN trial, although this did not discriminate between non-clear cell subtypes and results in further studies were modest. The National Institute for Care and Health Excellence has recently published new guidelines for the use of cabozantinib, which has shown evidence of improved progression-free survival and overall response rates compared with sunitinib. Unfortunately, many of the relevant studies did not specifically assess these treatments in patients solely with papillary renal cell carcinoma and had modest overall success. There is weak evidence that tyrosine kinase inhibitors give significant benefit in those patients with metastatic papillary renal cell carcinoma. Level of evidence: 2a