Treatment with Cabometyx before surgery in patients with advanced renal cell carcinoma, a type of kidney cancer, may provide benefits, although further research is required before a decision is made about its role in presurgical treatment.
Patients with locally advanced nonmetastatic clear-cell renal cell carcinoma (RCC) treated with Cabometyx (cabozantinib) before surgery had tumor reduction with no disease progression, based on findings from a recent analysis.
Dr. Mehmet A. Bilen, an associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta and director of the Genitourinary Medical Oncology Program at Winship Cancer Institute at Emory University, presented findings from this analysis at the 2022 ASCO Genitourinary Cancers Symposium. Results also demonstrated no life-threatening or fatal side effects related to treatment with Cabometyx.
“We showed that (Cabometyx) was clinically active and safe in the neoadjuvant (pre-surgical) setting in patients with locally advanced nonmetastatic clear-cell RCC,” Bilen said in an interview with CURE®.
Assessing Presurgical Treatment in RCC
Bilen mentioned that it was important for he and his colleagues to conduct this study especially for this specific patient population.
“Currently, there is no well-established neoadjuvant treatment in patients with locally advanced nonmetastatic kidney cancer,” he explained. “There are multiple potential utilities of presurgical treatment. For example, those patients have higher risk for recurrence, and this treatment might improve long-term outcome. It can convert the need of radial nephrectomy to partial nephrectomy. It can make surgery easier, potentially sparing organs. (Depending) on treatment, it can cause systemic effects and immune induction.”
In the analysis of this study, 17 patients with clear-cell RCC were treated with 60 milligrams of Cabometyx once per day for 12 weeks before undergoing surgery. Of the patients in the study, 82.4% were men with a median age of 58 years.
“In recent years, highly active treatment options become available for patients with metastatic renal cell carcinoma,” Bilen said. “The increased response rates with (Cabometyx) in metastatic renal cell carcinoma, along with the other neoadjuvant (tyrosine kinase inhibitor) data, we studied the role for (Cabometyx) in the neoadjuvant setting in this investigator-initiated clinical trial.”
The primary goal of this study was an objective response rate (a measurable response to treatment) at 12 weeks, including complete (the disappearance of all signs of cancer from treatment) and partial responses (a decrease in tumor size or the amount of cancer in the body from treatment). Secondary goals of this study included tolerability, safety, surgical outcome, clinical outcome and quality of life.
All patients had 12 weeks of treatment with Cabometyx, and most patients (16 patients) underwent surgery without delay after a four-week period when patients did not receive Cabometyx treatment. The one patient who did not undergo surgery refused the procedure for personal reasons and received further systemic treatment.
Results from this analysis demonstrated that all patients had tumor reduction. In particular, five patients had a partial response and 12 patients had stable disease (cancer that did not decrease or increase in severity). Progression of disease was not observed in the patients treated with Cabometyx. The primary renal tumor size was reduced by a median of 23%.
“Neoadjuvant treatment is well established in different solid tumors such as breast cancer, gastrointestinal cancers and others,” Bilen said. “Effective neoadjuvant treatment options are needed in patients with locally advanced RCC. We try to explore this in this population and show its feasibility. We are hoping with additional clinical trial data, we are able to establish the role of presurgical treatment in this patient population.”
At the end of treatment, one patient who was deemed to be unresectable (unable to be removed by surgery) at the start of the study was considered resectable after 12 weeks. Two patients also converted from radial nephrectomy (complete removal of a kidney, adrenal gland and lymph nodes) at the start of the study to partial nephrectomy (part of one kidney is removed during surgery) at the end of treatment.
Manageable Side Effects With Cabometyx
The most common side effects that occurred throughout treatment included anorexia, diarrhea, high blood pressure, fatigue and nausea. One serious side effect occurred that was related to a pulmonary embolism (the blockage of a blood vessel in the lung). Some dose reductions did occur as a result of some side effects; five patients decreased to a 40-milligram dose and two patients decreased to a 20-milligram dose. Two patients died at the time this analysis was performed, including one patient who died from COVID-19 and one patient who died from an unknown cause.
“A larger clinical trial is needed to further establish the role of presurgical treatment in RCC,” Bilen said. “This will allow us to understand the long-term role of those treatments. In addition to that, other agents such as immunotherapy combinations need to be studied in this space as well. Additionally, we also need to investigate the optimum duration of treatment, ideal clinical trial endpoints and additional correlative studies that will help us to understand the biology of RCC.”
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