Neoadjuvant cabozantinib clinically active in renal cell carcinoma


Findings from a phase 2 study shared during the 2022 ASCO Genitourinary Cancers Symposium showed that neoadjuvant cabozantinib (Cabometyx) was safe and induced a reduction in tumor size in all patients with locally advanced nonmetastatic clear cell renal cell carcinoma (RCC).1

Neoadjuvant cabozantinib (Cabometyx) contributed to tumor reduction with no disease progression in patients with locally advanced nonmetastatic clear cell renal cell carcinoma (RCC), according to findings from an analysis presented at the 2022 ASCO Genitourinary Cancers Symposium.

Mehmet A. Bilen, MD

Mehmet A. Bilen, MD

Results from the analysis, which were presented by Mehmet A. Bilen, MD, 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, also demonstrated no treatment-related grade 4 or grade 5 adverse events.

“We showed that cabozantinib was clinically active and safe in the neoadjuvant setting in patients with locally advanced nonmetastatic clear-cell RCC,” said Bilen.

In the analysis of this study (NCT04022343), 17 patients with biopsy-proven clear-cell RCC were treated with neoadjuvant cabozantinib at a starting dose of 60 mg once per day for 12 weeks. Of the patients in the study, 82.4% were men with a median age of 58 years (range: 42-86 years).

“In recent years, highly active treatment options become available for patients with metastatic renal cell carcinoma,” Bilen said. “The increased response rates with cabozantinib in metastatic renal cell carcinoma, along with the other neoadjuvant [tyrosine kinase inhibitor] data, we studied the role for cabozantinib in the neoadjuvant setting in this investigator-initiated clinical trial.”

The primary outcome of this study was an objective response rate at 12 weeks per RECIST v1.1, including complete and partial responses. Secondary outcomes included tolerability, safety, surgical outcome, clinical outcome (overall survival and disease-free survival) and quality of life.

All patients had 12 weeks of treatment with cabozantinib, and most patients (n = 16) underwent surgery without delay after completing a 4-week wash-out period. 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, 5 patients (29.4%) had a partial response (overall response rate = 0.29; 95% CI, 0.1-0.56) and 12 patients had stable disease. Progression of disease was not observed in the patients treated with cabozantinib. The primary renal tumor size was reduced by a median of 23% (range: 6-45).

“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, 1 patient who was deemed to be unresectable at the start of the study was considered resectable after 12 weeks. Two patients also converted from radial nephrectomy at the start of the study to partial nephrectomy at the end of treatment.

The most common adverse events that occurred throughout treatment included anorexia, diarrhea, hypertension, fatigue and nausea.One serious adverse event occurred that was related to a pulmonary embolism. Some dose reductions did occur as a result of some adverse events; 5 patients decreased to a 40-mg dose and 2 patients decreased to a 20-mg dose. Two patients died at the time this analysis was performed, including 1 patient who died from COVID-19 and 1 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.”


1. Bilen MA, Liu Y, Nazha B, et al. Phase 2 Study of Neoadjuvant Cabozantinib in Patients with Locally Advanced Non-metastatic Clear Cell Renal Cell Carcinoma. Presented at: 2022 ASCO Genitourinary Cancers Symposium; February 17-19, 2022; Abstract 340.

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