Robotic-assisted surgery with intraoperative radiation offers new hope to patients with local cancer recurrence
A clinical trial now underway at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute is expected to help shed light on the role of cytoreductive nephrectomy in metastatic renal cell carcinoma (mRCC) and the sequencing of mRCC treatments. Eric Singer, MD, MA, MS, director of the Division of Urologic Oncology in The Ohio State College of Medicine at the Ohio State Wexner Medical Center, is the co-principal investigator.
Treatment for mRCC has evolved significantly in recent decades, particularly in relation to cytoreductive nephrectomy (CN). The value of the surgery, once considered the standard of care in combination with systemic cytokines, has been called into question with the advent of newer medications such as systemic targeted therapies and immune-oncologic agents. In 2019, for instance, the CARMENA trial found that intermediate- and poor-risk patients taking sunitinib alone had better median overall survival than those taking the drug after CN (18.4 months vs. 13.9 months), though the validity of those results was questioned. Subsequent analysis showed that patients in the sunitinib alone group who underwent secondary CN – nearly a third of whom resumed sunitinib after surgery – had significantly better overall median survival compared to patients who didn’t have CN surgery (48.5 months vs. 15.7 months).
The SURTIME trial, which compared immediate CN followed by sunitinib with deferred surgery preceded by three cycles of the drug, also found a survival benefit for delayed CN. All of this has raised questions about the timing and sequence of mRCC treatments, including CN, and the selection of the most appropriate therapies for specific patients. With immune checkpoint inhibitors now a first-line therapy for mRCC, and the possibility of novel drug combinations, even more questions exist.
“Because there is much we don’t yet know about the optimal treatment for mRCC, clinical trials play a vital role in getting answers,” says Dr. Singer, who’s studied CN for years. “The hope is that this study will identify treatments that improve patients’ quality of life, further extend survival and potentially cure disease.”
Evaluating cabozantinib and nivolumab in combination with CN
Dr. Singer’s study is evaluating the effectiveness of providing cabozantinib and nivolumab to patients prior to CN. Specifically, he and his team are investigating whether the treatment protocol will increase the number of patients who show no evidence of disease at some point during the course of their treatment.
The study, known as the Cyto-KIK Trial – CYTO Reductive Surgery in Kidney Cancer Plus Immunotherapy (Nivolumab) and Targeted Kinase Inhibition (Cabozantinib) – began in June 2020 and will continue through May 2026. It’s currently recruiting patients, with the goal to enroll 48 participants. In addition to the Ohio State Wexner Medical Center, participating study sites include Rutgers Cancer Institute of New Jersey, Columbia University Irving Medical Center and Cleveland Clinic.
Participants must meet eligibility requirements, which include having:
- Radiographic evidence suggestive of mRCC (with subsequent pathologic confirmation of renal cell carcinoma with a clear cell component) or histological/cytological evidence of mRCC with a clear cell component
- Measurable tumor in the kidney
- No prior treatment for mRCC
All study participants receive both medications for 12 weeks. They take oral doses of cabozantinib daily and receive nivolumab intravenously every 28 days. Researchers will stop the cabozantinib 14 days before CN. Patients benefitting from their treatment may resume the medications following surgery.
The drugs may help prime the immune system to better attack cancer cells, Dr. Singer says. In combination with CN, that may lead to better overall treatment response.
Researchers hope to measure median size reduction of the primary tumor prior to surgery. In addition to looking for complete treatment response, for up to five years after treatment ends, they’ll evaluate:
- Overall survival
- Progression-free survival
- Response rate
- Surgical outcomes assessed by the Clavien-Dindo classification system
Clinical trial participation is vital
It’s known that CN is best performed in high-volume centers by high-volume surgeons, according to Dr. Singer. With as many as 17% of renal cell carcinoma patients having metastatic disease at the time of diagnosis, and up to 40% presenting initially with localized disease but eventually going on to develop mRCC, more definitive answers about optimal treatment are essential. Those answers will only come with clinical trials, which Ohio State helps advance in urology and all other areas of medicine.
Encouraging patients to participate in trials like this one is vitally important, Dr. Singer says. They help physicians make better treatment recommendations, help patients make more informed decisions and advance overall patient care.
For more information about the Cyto-KIK trial, email Dr. Singer at Eric.Singer@osumc.edu.
