Most US Oncologists Choose mTOR Inhibitor as Second Therapy in mccRCC

Charles J. Ryan, MD

Most medical oncologists in the United States would opt for an mTOR (mammalian target of rapamycin) inhibitor as second-line therapy for patients with metastatic clear cell renal cell carcinoma (mccRCC). The finding, from a case-based market research study, was presented by Charles J. Ryan, MD, associate professor of Clinical Medicine in Urology, University of California at San Francisco, at the 2014 Genitourinary Cancers Symposium.

“We looked at what is happening with community oncologists and this is survey data that we have collected from community oncologist both in the setting of renal cell cancer as well as prostate cancer,” Ryan said. “The attempt was to describe the context in which the local physicians would prescribe a given therapeutic.”

Ryan and colleagues used a case-based research tool to assess the preferences of 338 US medical oncologists for second-line therapy in patients with mccRCC who were managed with a tyrosine kinase inhibitor (TKI) as first-line therapy. The oncologists were offered four choices for second-line therapy based on an mccRCC core case scenario with 3 variant first-line TKI therapy outcomes: objective response, stable disease, and progressive disease. The hypothetical patient’s relevant history, physical examination, laboratory values, and imaging data were provided. Up to 10 second-line treatment options were offered for each scenario variant being tested. Each medical oncologist selected his/her most preferred second-line prescribing preference from the available options. Prescribing preferences for second-line therapy were evaluated across four different scenarios based on the initial TKI prescribed and the magnitude and duration of response to initial therapy.

The core case was as follows: A 43-year-old man with recurrent disease in lung and bone 4 years after nephrectomy for ccRCC. His Eastern Cooperative Oncology performance status is 1. There are no central nervous system metastases. His creatinine clearance is 79 m/Lmin.

The scenarios tested were:

• Scenario 1: 9-month objective partial response with sunitinib as first-line therapy
• Scenario 2: 9-month objective response with pazopanib as first-line therapy
• Scenario 3: 4 months stable disease with pazopanib as first-line therapy
• Scenario 4: Progression at 8 weeks with sunitinib as first-line therapy

An mTOR agent was chosen as second-line therapy by 51%, 62%, 82%, and 79% of respondents for scenarios 1 through 4, respectively. Everolimus was preferred over temsirolimus in all four scenarios: 29% vs 22% in scenario 1, 37% vs 25% in scenario 2, 60% vs 22% in scenario 3, and 49% vs 30% in scenario 4.

“In kidney cancer, we found a strong preference for community oncologist in the second-line setting to prescribe mTOR therapies, and that is certainly supported by the literature and certainly supported by the regulatory approvals of given agents,” Ryan said. “What’s a little different is that there may be different contexts in which prescribing patterns evolved. I found it to be interesting data. It is worth having out there for those of us to see how community oncologists think and act.”

A TKI was chosen as second-line therapy by 46% in scenario 1 and 35% in scenario 2 (extended partial response), 15% in scenario 3, and 16% in scenario 4. No specific TKI was the dominant preference in this first salvage setting.

Ryan acknowledges that there are many considerations when considering therapies for RCC, including toxicity, extent of disease, and issues regarding nephrectomies. “Many clinicians initiate TKI therapy from which there is no benefit received by the patient,” he said. “They may be more likely to switch to a different class. The question that comes to mind is what was the experience with the initial TKI.”

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