Translating new data to the daily practice in second line treatment of renal cell carcinoma: The role of tumor growth rate

Abstract

The therapeutic options for patients with metastatic renal cell carcinoma (mRCC) have completely changed during the last ten years. With the sequential use of targeted therapies, median overall survival has increased in daily practice and now it is not uncommon to see patients surviving kidney cancer for more than four to five years. Once treatment fails with the first line targeted therapy, head to head comparisons have shown that cabozantinib, nivolumab and the combination of lenvatinib plus everolimus are more effective than everolimus alone and that axitinib is more active than sorafenib. Unfortunately, it is very unlikely that we will ever have prospective data comparing the activity of axitinib, cabozantinib, lenvatinib or nivolumab. It is frustrating to observe the lack of biomarkers that we have in this field, thus there is no firm recommendation about the optimal sequence of treatment in the second line. In the absence of reliable biomarkers, there are several clinical endpoints that can help physicians to make decisions for an individual patient, such as the tumor burden, the expected response rate and the time to achieve the response to each agent, the prior response to the agent administered, the toxicity profile of the different compounds and patient preference. Here, we propose the introduction of the tumor-growth rate (TGR) during first-line treatment as a new tool to be used to select the second line strategy in mRCC. The rapidness of TGR before the onset of the treatment reflects the variability between patients in terms of tumor growth kinetics and it could be a surrogate marker of tumor aggressiveness that may guide treatment decisions.

Keywords: Axitinib; Everolimus; Cabozantinib; Kidney cancer; Nivolumab; Renal cell; Sequence; Second line; Sorafenib; Tumor-growth rate

Core tip: The landscape of renal cell carcinoma has dramatically changed in the last decade. Today, at least 6 agents are approved after failure with cytokines, sunitinib or pazopanib in first line treatment. Lack of reliable biomarkers to select the best treatment in daily practice is somewhat frustrating. Therefore, our decisions in real practice are based on safety profiles, patient’ co-morbidities and physician experience or preference. Here we debate the pros and cons of the tumor-growth rate as a tool to select second line systemic treatment after failure to a prior tyrosine kinase-inhibitor in patients with advanced renal cell carcinoma.