The advent of targeted therapies in the last decade has led to improved management of renal cancer and is now considered the mainstay of therapy for mRCC. FDA-approved targeted therapies include multi-targeted TKIs (tyrosine kinase inhibitors) sunitinib, sorafenib, axitinib, and pazopanib; mTOR (mammalian target of rapamycin kinase) inhibitors temsirolimus and everolimus; and VEGF (vascular endothelial growth factor) inhibitor bevacizumab in combination with interferon alfa. These agents work by targeting different signaling pathways that are affected in cancer patients. Objective responses, mostly partial responses, have been reported in 8% to 39% of patients treated with targeted therapies, and overall survival of more than two years with sunitinib and VEGF-targeted therapy has been observed.4,5
The question remains as to whether or not these targeted therapies should be continued as maintenance therapy in patients who achieve a response. While prolonged therapy with TKIs leading to response has been demonstrated, there are significant concerns as to the safety and efficacy of using this approach. Arguments for continuing treatment include preventing disease recurrence due to residual cancer cells, possible rebound effect with fast regrowth and metastasis. However, discontinuing therapy may lead to less toxicity (including fatigue, GI symptoms, skin toxicities, and hand-foot syndrome), reduced risk of developing resistant cancer cells, and an opportunity to maintain healthcare costs.4
Two recently published studies have demonstrated that stopping therapy after patients achieve a complete response may, in fact, be beneficial.4,5 A retrospective analysis conducted by Albiges and colleagues examined the characteristics of patients with mRCC who achieved a complete response (CR) while treated with a TKI. The authors also investigated the effect of discontinuing targeted therapy on overall patient outcome. This analysis included 64 patients who experienced CR during treatment with either sunitinib (n=59) or sorafenib (n=5). Out of 36 patients who achieved CR with TKI treatment alone, 28 patients discontinued treatment, and 17 of the 28 patients (61%) remained in CR after a median follow-up of 255 days. Out of 28 patients treated with TKI in addition to either surgery or radiation, 25 patients discontinued treatment and 12 of the 25 patients (48%) remained in CR with a median follow-up of 322 days.
Furthermore, patients who relapsed after TKI discontinuation remained sensitive to targeted therapy when re-challenged with systemic targeted therapy. Out of 24 patients who relapsed after discontinuation, 11 patients received further treatment with the same TKI, and 4 patients were treated with a different targeted therapy (3 with a TKI and 1 with bevacizumab). Of these, 11 patients achieved partial response (PR) (n=8) or stable disease (SD0 (n=3). Predictive factors to help guide which patients are better candidates for stopping or continuing therapy were not identified.4