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Johns Hopkins Pediatric

Treating High-Risk Kidney Cancer Before it Spreads



Is it a question of timing? Should we try the drug even earlier? “When cancer is localized within the kidney, nephrectomy (kidney removal) is the treatment of choice,” says Mohamad Allaf, M.D. However, surgery alone is not enough for all patients diagnosed with localized kidney cancer. In about one-third of patients, cancer comes back and spreads beyond the kidney.

Allaf is hoping to change this statistic by hitting the cancer even harder at the beginning. “Drugs called immune checkpoint inhibitors (ICI) have improved the outcomes of patients with metastatic kidney cancer,” he says. “What if we gave these ICIs to patients around the time of surgery – when the disease is still localized – to help decrease their chances of recurrence?”

Allaf recently led the multi-center phase III PROSPER RCC trial, in which nearly 900 patients with RCC were randomly assigned either to receive the ICI drug nivolumab or no drug at the time of nephrectomy. “Unfortunately, this trial found no benefit in giving nivolumab in this setting – but fortunately, this was the first phase III ICI trial of its kind in RCC.”

In other words, it was a start, and we can learn from it. Allaf and colleagues collected “droves of biological specimens and data” from this trial. Then they and others wondered: Is it a question of timing? Should we try the drug even earlier?

And so they did. Allaf then led the first prospective trial of nivolumab before surgery for patients with high-risk localized RCC – cancer that is likely to come back and to spread – at Johns Hopkins. “We showed that nephrectomy after nivolumab is safe and feasible.”

Nirmish Singla, M.D., M.Sc., recently analyzed blood and tissue samples acquired from this phase I trial. He found important relationships between immune cells within the tumor microenvironment and response to ICI. “We also found changes within the primary tumor and in the circulation that were induced by nivolumab treatment, and these provide support for more perioperative (before surgery) ICI approaches in the future, perhaps in combination with other ICI drugs.”

Allaf presented the clinical results from the PROSPER RCC trial at the 2022 European Society for Medical Oncology (ESMO) Congress in Paris, and Singla then presented the correlative results from the phase I trial at the 2023 American Urological Association (AUA) Annual Meeting in Chicago. Singla also serves as the Principal Investigator of a translational research grant awarded by the Department of Defense to further study the effects of ICI on primary tumors in RCC.

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