How Can Second-Line Therapy for Metastatic Renal Cell Carcinoma Help to Define an Overall Management Strategy?

Abstract

For many years, therapy for metastatic renal cell carcinoma (mRCC) was limited to a single line of cytokine therapy with either interferon or interleukin-2. Relatively recently, the novel targeted agents bevacizumab, sorafenib, sunitinib and temsirolimus have each demonstrated activity in patients with mRCC that is refractory to cytokine therapy. Based on phase III trial data of patients who have received no prior therapy for mRCC, targeted agents have now rapidly replaced cytokines or, in the case of bevacizumab, are used in combination with interferon as first-line therapy for mRCC. Thus, second-line therapy for mRCC needs to be re-evaluated. Available data indicate that patients whose disease is refractory to a targeted agent may obtain, in some cases, benefit from a different agent, inhibiting either the same or a different pathway. With the availability of relatively few drugs for the treatment of mRCC, it is important to consider how to ensure that patients are obtaining maximum benefit through optimal use of the agents available. The definition of whether second-line therapy is active and tolerable and which therapy should be used in this setting in individual patients, particularly taking into account prior therapy, will therefore be important in defining the general therapeutic strategy in patients with mRCC.

Overall survival in patients with metastatic renal cell carcinoma initially treated with bevacizumab plus interferon‐α2a and subsequent therapy with tyrosine kinase inhibitors: a retrospective analysis of the phase III AVOREN trial

“…Thus, several rational approaches to sequencing have been proposed based on published data [40,41]. These include first‐line bevacizumab + IFN followed by sorafenib/sunitinib or sunitinib/sorafenib and finally everolimus; this approach also allows for the use of all agents with proven efficacy in mRCC.…”

Indirect treatment comparison of bevacizumab + interferon-α-2a vs tyrosine kinase inhibitors in first-line metastatic renal cell carcinoma therapy

“…In addition, there are first retrospective analyses indicating that BEV+IFN first-line enables effective subsequent TKI therapy,6,32 which may lead to improved patient outcomes, taking into account the complete sequence of mRCC therapies 33,34…”