Switching Therapies for Progressive Advanced RCC

Following progression on first-line therapy, patients with renal cell carcinoma (RCC) often do not need to be hurried to second-line treatment, says David F. McDermott, MD. If there is existing disease that is not harming the patient, and the patient feels well, there is no reason to switch therapies, adds Eric Jonasch, MD.

When determining the best time to switch therapies, it is important to remember that a percentage increase on imaging evaluation does not strictly define disease progression in RCC, notes McDermott. However, symptomatic progression indicates that it may be an appropriate time to adjust treatment.

The ultimate objective for the patient is to prolong survival with the best quality of life, comments Thomas Hutson, DO, PharmD. If this is accomplished and the disease is not spreading to new areas, the current treatment can be continued, says Hutson. Goals of therapy shift for the patients as they move from first-line to second-, third-, and fourth-line therapies. In first-line treatment, patients want efficacy and are willing to compromise side effects for tumor shrinkage. In later lines of therapy, there is less focus on tumor shrinkage and more on achieving stable disease, notes Hutson.

When selecting a second-line therapy, both VEGF and mTOR inhibition is acceptable. The AXIS trial demonstrated that axitinib, a VEGF receptor inhibitor, is effective as a second-line therapy. Additionally, the RECORD-1 trial showed that patients with metastatic RCC who had been treated with a VEGF inhibitor had improvement in progression-free survival with mTOR inhibition.

Data support that kidney cancer is a VEGF-driven disease, and many clinicians want to stay in that drug class for that reason, says McDermott. Defining the small subset who benefit from mTOR inhibition is essential, adds McDermott, because there are patients who achieve durable responses and feel better with mTOR therapy. Investigators may be able to look into tumor gene expression to help predict who might be more sensitive to mTOR inhibition.

There is some evidence that VEGF therapy followed by another VEGF agent may be an appropriate strategy, explains Hutson, as it has shown to produce greater benefit to patients than VEGF followed by mTOR inhibition. The efficacy of mTOR inhibitors is not lost when it is pushed to a later line, adds Hutson.