Patient Approach in Advanced/Metastatic Renal Cell Carcinoma
Recent therapeutic advances have changed the treatment landscape of metastatic renal cell carcinoma. Unfortunately, the seven agents now available are not based on biomarkers that would indicate which one could provide the best benefit for every patient. We have reviewed the available information concerning the impact of each treatment on comorbidities or status that are frequently seen before commencing treatment for the advanced disease: elderly and patients with cardiovascular complications, metabolic and endocrinology disorders, and infections, as well as impaired organ function (kidney, liver and heart). Additional new drugs will be launched, but no predictive biomarkers are available. Head-to-head studies to evaluate the safety of the different drugs are rare. In this quite complex scenario, we believe that a decision-making approach focused on the patient may represent a suitable strategy.
Until recently, immunotherapy was the only treatment available for metastatic renal cell carcinoma (mRCC). Following the introduction in the oncology therapeutic setting of the new-targeted agents, the oral active multikinase inhibitors (tyrosine kinase inhibitors; TKIs) sorafenib and sunitinib have represented a breaking point and a fundamental step forward in the treatment of mRCC. Paradoxically, we now have plenty of choice thanks to the long-awaited availability of seven new therapeutic approaches that have dramatically changed the possibility of treating this disease. Following approval by the US FDA and EMA in 2006 of sorafenib and sunitinib, which were the first two TKIs used for the treatment of mRCC, other different and important agents, such as mTOR inhibitors temsirolimus and everolimus, the monoclonal VEGF antibody bevacizumab, and, more recently, the two TKIs pazopanib and axitinib, have widened the therapeutic armamentarium.
Unfortunately, often these targeted therapies are not curative for mRCC patients. Despite considerable delayed tumor progression, complete and long-lasting responses are observed in less than 1% of cases. Analyses of different studies have shown that no targeted agent seems to be superior to another in terms of overall survival in a first-line setting. In this situation, it is likely that a strategy based on the administration of the most suitable agent for a patient, with the aim of assuring the best compliance, could offer a good quality of life while improving efficacy. To reach this goal, the patient must be considered as the center of the decision-making process, rather than planning a sequential strategy for all patients. Of note, a large proportion of mRCC patients are elderly and often present with a number of comorbidities; therefore, we believe that special recommendations on how to best manage elderly patients in clinical practice are required.
In our opinion, a strategy that is not only based on guidelines and algorithms but that also highlights the clinical evaluation of the patient may be considered in the decision-making process. We have analyzed data from literature and matched them with the experience gained at our institution in daily clinical practice. We took into consideration information concerning age and comorbidities of the patients, and the toxicity profile of every agent.
Abstract and Introduction
Abstract
Recent therapeutic advances have changed the treatment landscape of metastatic renal cell carcinoma. Unfortunately, the seven agents now available are not based on biomarkers that would indicate which one could provide the best benefit for every patient. We have reviewed the available information concerning the impact of each treatment on comorbidities or status that are frequently seen before commencing treatment for the advanced disease: elderly and patients with cardiovascular complications, metabolic and endocrinology disorders, and infections, as well as impaired organ function (kidney, liver and heart). Additional new drugs will be launched, but no predictive biomarkers are available. Head-to-head studies to evaluate the safety of the different drugs are rare. In this quite complex scenario, we believe that a decision-making approach focused on the patient may represent a suitable strategy.
Introduction
Until recently, immunotherapy was the only treatment available for metastatic renal cell carcinoma (mRCC). Following the introduction in the oncology therapeutic setting of the new-targeted agents, the oral active multikinase inhibitors (tyrosine kinase inhibitors; TKIs) sorafenib and sunitinib have represented a breaking point and a fundamental step forward in the treatment of mRCC. Paradoxically, we now have plenty of choice thanks to the long-awaited availability of seven new therapeutic approaches that have dramatically changed the possibility of treating this disease. Following approval by the US FDA and EMA in 2006 of sorafenib and sunitinib, which were the first two TKIs used for the treatment of mRCC, other different and important agents, such as mTOR inhibitors temsirolimus and everolimus, the monoclonal VEGF antibody bevacizumab, and, more recently, the two TKIs pazopanib and axitinib, have widened the therapeutic armamentarium.
Unfortunately, often these targeted therapies are not curative for mRCC patients. Despite considerable delayed tumor progression, complete and long-lasting responses are observed in less than 1% of cases. Analyses of different studies have shown that no targeted agent seems to be superior to another in terms of overall survival in a first-line setting. In this situation, it is likely that a strategy based on the administration of the most suitable agent for a patient, with the aim of assuring the best compliance, could offer a good quality of life while improving efficacy. To reach this goal, the patient must be considered as the center of the decision-making process, rather than planning a sequential strategy for all patients. Of note, a large proportion of mRCC patients are elderly and often present with a number of comorbidities; therefore, we believe that special recommendations on how to best manage elderly patients in clinical practice are required.
In our opinion, a strategy that is not only based on guidelines and algorithms but that also highlights the clinical evaluation of the patient may be considered in the decision-making process. We have analyzed data from literature and matched them with the experience gained at our institution in daily clinical practice. We took into consideration information concerning age and comorbidities of the patients, and the toxicity profile of every agent.
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