Dr. Harshman on the PROTECT Trial in Patients With Locally Advanced RCC

Lauren C. Harshman, MD, assistant professor of medicine, Harvard Medical School, senior physician, Dana-Farber Cancer Institute, discusses how the PROTECT trial sought to answer the controversial results of the ASSURE and S-TRAC trials.

ASSURE was a large study that randomized patients to sunitinib (Sutent) with placebo, sorafenib (Nexavar) with placebo, or placebo with placebo. Patients had lower-stage disease or non-clear cell RCC. The S-TRAC trial focused on a very high-risk subset of patients with clear cell RCC. The ASSURE trial didn’t show a benefit in disease-free survival (DFS) or overall survival (OS) compared with placebo, whereas the S-TRAC trial showed a DFS benefit at more than 1 year with adjuvant sunitinib compared with placebo.

The PROTECT trial had elements that supported both approaches. The study did not meet its primary endpoint. It was amended to look at DFS in the 600-mg subset once the dose of pazopanib (Votrient) was decreased to account for liver toxicity. The subset of patients who received the full dose of 800 mg did see a benefit in DFS. That may be a case to support the use of adjuvant tyrosine kinase inhibitor therapy, says Harshman.