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Combination strategies represent an established treatment paradigm that has resulted in cures for patients with lymphoma and testicular cancer. To explore this approach further in metastatic renal cell carcinoma (mRCC), the phase IIIb INTORACT study compared first-line bevacizumab and temsirolimus to the FDA approved combination of interferon plus bevacizumab.
This trial was based on preliminary data suggesting the combinations of a VEGF and mTOR inhibitor was efficacious, explains Brian I. Rini, MD. However, results from the INTORACT study showed that both arms were equivalent with a median progression-free survival of around 9 months. Moreover, Rini adds, more side effects were associated with the bevacizumab and temsirolimus combination. Considering these and other data, Robert A. Figlin, MD, notes that he remains unsure of the most optimal setting for bevacizumab administration.
The clinical development of bevacizumab in mRCC has been unique, Rini notes. When the agent was initially developed interferon was the standard of care, resulting in the investigation of the combination of interferon and bevacizumab. However, a growing body of evidence is now supporting the single-agent use of bevacizumab in the frontline setting, Rini notes.
At this point in time, Rini explains, a distinct population of patients may be ideal for treatment with bevacizumab in the frontline setting. These patients include those who have trouble receiving oral medications and elderly patients who may not tolerated the side effects associated with TKIs. Additionally, since more evidence is supporting single-agent bevacizumab, Rini suggests administering interferon at a lower-dose and eventually omitting it from the combination to help better manage side effects.
One of the main challenges facing the widespread utilization of bevacizumab is an overall lack of level 1 evidence to support its single-agent use, believes Eric Jonasch, MD. Adding to this, bevacizumab is administered intravenously and other agents are subcutaneous or oral. However, Jonasch notes, there are special circumstances where treatment with bevacizumab may be ideal, based on side effect profiles. The agent administered can be tailored to fit each patient, Figlin agrees, since several agents with similar efficacy are available in the frontline setting.
From a community oncologist perspective, Thomas E. Hutson, DO, PharmD, suggests that bevacizumab is under utilized and under recognized in the community setting. In general, many of the newer oral agents are used more frequently, largely, Hutson believes, as a result of a lack of recognition of bevacizumab as a viable treatment option.