RCC sequencing: One good answer

Molecularly targeted therapy has become standard treatment for advanced renal cell carcinoma (RCC). Many new agents such as axitinib (Inlyta), everolimus (Afinitor), pazopanib (Votrient), sorafenib (Nexavar), sunitinib (Sutent), and temsirolimus (Torisel) are now approved for this indication. These agents inhibit either vascular endothelial growth factor or tyrosine kinase pathways.

Sorafenib and sunitinib are the most commonly used oral agents for metastatic RCC. The optimum sequence of these two agents has not been prospectively studied.

The SWITCH trial presented at the 2014 Genitourinary Cancers Symposium studied the sequencing of either sorafenib or sunitinib as first- or second-line therapy. The order did not affect progression-free or overall survival for patients with metastatic RCC. Adverse events were as expected, although there was a suggestion that side effects were less with second-line use of either drug. The SWITCH trial was designed to demonstrate that one of the sequences would be superior. While results failed to demonstrate superiority of either, the trial did answer an important sequencing question.

This challenge of optimum sequencing is not unique to RCC. We face similar challenges with multiple new agents available for metastatic castration-resistant prostate cancer.

The take-home message is that for sorafenib and sunitinib, sequencing does not appear to be drug dependent and either can be used as first- or second-line therapy. This study also demonstrated an overall survival of 30 months, one of the highest reported in this disease state.

While these newer targeted therapies have become the “go-to” drugs for advanced disease, immunotherapy remains a viable option for many patients. As we embrace targeted therapies, the fact that immunotherapy can induce long-term complete remissions in up to 10% of patients is something not seen with these newer agents. More work is needed in terms of sequencing all targeted and traditional immunotherapies in advanced RCC. For now, SWITCH suggests either sorafenib or sunitinib can be considered as initial therapy with either a reasonable second-line choice.UT

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