Lauren C. Harshman, MD
Although the S-TRAC trial showed a disease-free survival (DFS) benefit at more than 1 year with adjuvant sunitinib (Sutent), Lauren C. Harshman, MD, says that patients with high-risk clear cell renal cell carcinoma (RCC) could still develop recurrence. Therefore, studies of adjuvant immunotherapy offer an exciting alternative.
State of the Science Summit™ on Genitourinary Cancers, Harshman, assistant professor of medicine, Harvard Medical School, senior physician, Dana-Farber Cancer Institute, weighed the advantages and disadvantages of emerging adjuvant therapies, and she discussed ongoing clinical trials examining the incorporation of immune therapies into practice.
OncLive: What are the latest adjuvant treatments in high-risk RCC?
In terms of nonmetastatic RCC, we are in the early stages of developing something better than nephrectomy alone. The standard of care today remains surgical removal of the primary tumor. A large number of patients, especially those with higher-stage disease—T3, T4, or clinical node-positive disease—have a very high risk of recurrence. There have been 40 years of investigation with various drugs in the metastatic setting that were effective or minimally effective. We have since moved them forward, and the 1 positive trial—S-TRAC, with sunitinib—was countered by the negative ASSURE trial.
The PROSPER study is looking at a novel way, or adjuvant therapy “with a twist,” of giving a couple of doses of PD-1 priming blockade to rev up the immune system. When you have a significant amount of androgen in place, you can build a T-cell effector army to then take out the tumor. This is followed by 9 months of adjuvant nivolumab to sustain the immune system and work against micrometastatic disease, which is the real killer.
Can you discuss results of the ASSURE and S-TRAC trials?
The controversy stems from the fact that we have 2 big trials with the same drug and disparate results. The ASSURE trial was a large study that randomized more than 1900 patients to sunitinib with placebo, sorafenib with placebo, or placebo with placebo. Patients had lowerstage 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 DFS or OS compared with placebo, whereas the S-TRAC trial showed a DFS benefit at more than 1 year with adjuvant sunitinib compared with placebo.
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