Cabozantinib is an oral multikinase inhibitor approved for treatment in metastatic renal cell carcinoma (RCC). We conducted a phase 2, nonrandomized, single-arm clinical trial (NCT04022343) of cabozantinib treatment for 12 weeks in 17 patients with locally advanced, biopsy-proven, nonmetastatic clear cell RCC before surgical resection. The primary end point was the objective response rate (complete and partial responses) at week 12 and secondary end points included safety, tolerability, clinical and surgical outcomes, and quality of life. Six patients (35%) experienced a partial response and 11 patients (65%) had stable disease. The most common adverse events were diarrhea (n = 12, 70.6%), anorexia, fatigue and hypertension (n = 10, 58.8%), nausea and palmar-plantar erythrodysesthesia syndrome (n = 9, 52.9%). No treatment grade 4 or 5 adverse events related to cabozantinib or surgery occurred. The 1-year disease-free survival and overall survival were 82.4% (95% CI 54.7-93.9%) and 94.1% (95% CI 65-99.1%), respectively. Cabozantinib treatment activated CD8+ T cells in the blood, depleted myeloid populations and induced immune niches for TCF1+ stem-like CD8+ T cells. Cabozantinib was clinically active and safe in the neoadjuvant setting in patients with locally advanced nonmetastatic clear cell RCC.
Nature cancer. 2025 Feb 27 [Epub ahead of print]
Mehmet A Bilen, BaoHan T Vo, Yuan Liu, Rachel Greenwald, Amir H Davarpanah, Donald McGuire, Rakesh Shiradkar, Liping Li, Adhishek Midya, Bassel Nazha, Jacqueline T Brown, Sierra Williams, Wilena Session, Greta Russler, Sarah Caulfield, Shreyas S Joshi, Vikram M Narayan, Christopher P Filson, Kenneth Ogan, Omer Kucuk, Bradley Curtis Carthon, Luke Del Balzo, Athena Cohen, Adriana Boyanton, Nataliya Prokhnevska, Maria Andrea Cardenas, Ewelina Sobierajska, Caroline S Jansen, Dattatraya H Patil, Edouard Nicaise, Adeboye O Osunkoya, Haydn T Kissick, Viraj A Master
Winship Cancer Institute of Emory University, Atlanta, GA, USA. ., Department of Urology, Emory University School of Medicine, Atlanta, GA, USA., Winship Cancer Institute of Emory University, Atlanta, GA, USA., Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA., Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA., Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA., Winship Cancer Institute of Emory University, Atlanta, GA, USA. ., Winship Cancer Institute of Emory University, Atlanta, GA, USA. .