Second-line systemic therapy for the treatment of metastatic renal cell cancer

Abstract

The discovery of molecular mechanisms driving the progression of renal cell carcinoma (RCC) has led to the development of drugs that target RCC at the molecular level. Inhibition of VEGF-targeting pathways is successful as a front-line treatment in patients with metastatic RCC. In addition, bevacizumab/IFN-α, sunitinib and pazopanib are recommended for first-line use in good- or intermediate-risk patients, whereas temsirolimus is approved for poor-risk patients. Second-line options are valuable as these patients eventually progress. The present review addresses which drug is best in this second-line setting. Options for sequential therapy include tyrosine kinase inhibitor (TKI)-mTOR inhibitor or TKI-TKI sequences. We also address the question of whether sequential therapy with TKIs or the combination of VEGF followed by mTOR inhibition is the best choice for specific patients, and which sequence of TKIs is most beneficial.

Real-world dosing and drug costs with everolimus or axitinib as second targeted therapies for advanced renal cell carcinoma: a retrospective chart review in the US

“…Although not directly assessing dose intensity, our current findings did show that, compared to patients treated with everolimus, those treated with axitinib were more likely to initiate therapy at a higher-than-recommended dose and were more likely to dose escalate. Together with the modeling study by Perrin et al 19 , the current findings indicate that everolimus might be a less costly option in routine clinical practice relative to axitinib, which provide additional real-world evidence to help decisionmaking regarding the optimal treatment sequencing for aRCC [26][27][28][29][30] . This study is subject to several limitations, some of which are inherent to retrospective reviews of medical chart data.…”

Impact of an Altered Wnt1/β-Catenin Expression on Clinicopathology and Prognosis in Clear Cell Renal Cell Carcinoma

“…These treatments improved patients’ median overall survival up to 26 months, but prognosis is still limited, as long-term responders are rare. Therefore, there is the definitive need for the improvement of therapeutic concepts, since progressive disease will develop, due to the inevitable development of a multi-drug resistance in metastatic renal cell carcinoma (mRCC) patients [2]. For future therapies of mRCC, the Wnt/β-catenin pathway, as a key regulator of cellular homeostasis in adult tissues and cell-to-cell interactions during embryogenesis, was proposed as a promising candidate [3–9].…”

A Rare Case of Synchronous Renal Cell Carcinoma of the Bladder Presenting with Gross Hematuria

“…The restaging showed a progressive pulmonal and bone metastatic disease without recurrence of the bladder lesion ten weeks after the start of systemic therapy. Due to lack of evidence-based second line treatment after mTOR based therapy failure, the therapy was switched to sunitinib malate 50 mg daily on a 4-weeks-on/2-weeks-off schedule 11 . The patient presented in reduced general conditions with ascites, general anasarca and symptoms of a paralytic ileus 6 weeks after the start of sunitinib malate.…”