Winship researchers find cabozantinib, a targeted therapy currently approved for advanced kidney cancer, may offer significant benefits when used before surgery in patients with locally advanced, nonmetastatic clear cell renal cell carcinoma.
Mehmet Asim Bilen, MD
A phase 2 clinical trial led by researchers at Winship Cancer Institute of Emory University has demonstrated that cabozantinib, a targeted therapy currently approved for advanced kidney cancer, may offer significant benefits when used before surgery in patients with locally advanced, nonmetastatic clear cell renal cell carcinoma (ccRCC).
The findings, published in Nature Cancer, suggest that cabozantinib not only shrinks tumors but also enhances immune activity within the tumor microenvironment—challenging traditional views on neoadjuvant therapy, which is treatment given before surgery to help shrink tumors and improve surgical outcomes.
“This study represents a critical shift in the way we think about pre-surgical treatment for kidney cancer,” says the study’s corresponding author Mehmet A. Bilen, MD, director of the Genitourinary Medical Oncology Program at Winship Cancer Institute of Emory University and associate professor in the Department of Hematology and Medical Oncology at the Emory University School of Medicine. “Cabozantinib doesn’t just shrink tumors—it actively reshapes the immune landscape, creating an environment that could improve long-term disease control and patient survival.”
BaoHan T. Vo, PhD, co-first author and researcher in the Emory Department of Urology, emphasized the study’s role in bridging clinical and translational science. “Our findings not only demonstrate cabozantinib’s efficacy in reducing tumor size but also reveal its impact on the immune system, reinforcing the potential for integrating immunotherapy into neoadjuvant strategies.”
Key Findings: Dual Benefits of Cabozantinib
The study, which enrolled 17 patients with locally advanced ccRCC, evaluated the effects of 12 weeks of cabozantinib before surgery. The results showed:
- 35% of patients (6 of 17) had a partial response, and 65% (11 of 17) had stable disease.
- One previously inoperable tumor became resectable, and two patients were able to undergo nephron-sparing surgery instead of full kidney removal.
- Tumors showed increased infiltration of CD8+ T cells, including TCF1+ stem-like CD8+ T cells, which are associated with better responses to immunotherapy.
- No major safety concerns were observed, and surgery remained feasible without complications despite preoperative treatment.
“These findings challenge the prevailing idea that neoadjuvant therapy is only about shrinking tumors,” says Bilen. “We are seeing evidence that it may also prime the immune system, potentially leading to better long-term outcomes.”
Hope for Patients with High-Risk Kidney Cancer
Viraj Master, MD, PhD
Approximately 50% of patients with locally advanced ccRCC experience recurrence within three years after surgery, underscoring the need for strategies that improve long-term disease control. This research suggests that cabozantinib may not only improve surgical outcomes but also enhance the immune response to cancer, potentially reducing recurrence rates.
“For some patients, neoadjuvant cabozantinib could mean the difference between an inoperable tumor and the chance for curative-intent surgery,” says Viraj A. Master, MD, PhD, a co-author, director of integrative oncology and survivorship at Winship Cancer Institute, and director of clinical research at Emory University School of Medicine’s Department of Urology.
Additionally, the findings lay the foundation for future combination strategies, particularly pairing cabozantinib with checkpoint inhibitors to optimize treatment response.
Next Steps: Expanding the Impact of Neoadjuvant Therapy
Building on these findings, researchers at Winship and Emory are pursuing larger clinical trials to evaluate:
- Cabozantinib alone versus combination approaches with immune checkpoint inhibitors.
- Long-term immune effects, assessing whether the immune activation seen before surgery translates into better survival outcomes.
- Biomarker-driven patient selection, using circulating tumor DNA (ctDNA), cytokine profiles and radiomic signatures to personalize treatment. This will help researchers determine which patients will benefit the most from this treatment. By analyzing small fragments of tumor DNA in the blood (circulating tumor DNA), measuring proteins linked to immune response (cytokines), and using advanced imaging techniques (radiomics), they hope to create a more personalized approach to treatment.
- Potential expansion to other cancers, exploring whether similar immune-modulating benefits can be seen in other solid tumors.
A New Paradigm for Kidney Cancer Treatment?
The study’s findings reinforce the idea that pre-surgical treatments can do more than just shrink tumors—they can shape the body’s immune response for long-term benefit. If validated in larger trials, this approach could change the standard of care for high-risk kidney cancer patients and open new avenues for combination therapies.
“This is an exciting step forward for the field of kidney cancer treatment,” says Bilen. “Our next goal is to build on this success through larger trials and further investigation into the role of immune priming in neoadjuvant therapy.”
A Multidisciplinary Effort at Winship
Haydn T. Kissick, PhD
The study was a collaborative effort involving experts across multiple disciplines, including medical oncology, urology, radiology, pathology and immunology, whose collective contributions were instrumental in advancing this research. For the comprehensive list of co-authors, please refer to the publication in Nature Cancer.
Researchers from Emory University School of Medicine’s Department of Urology and the Emory Vaccine Center contributed critical insights into tumor response, imaging-based biomarkers and immune profiling.
“This study builds on prior research at Emory, including investigations into immune niches within kidney tumors and the role of pre-surgical interventions in enhancing long-term immune responses,” says Master.
Notably, the study extends previous findings from Winship’s work on tumor immunology, including research by co-author Haydn T. Kissick, PhD, who also previously authored a 2019 Nature study that identified key immune mechanisms in renal cell carcinoma.
This research is supported by the National Cancer Institute of the National Institutes of Health under award numbers P30CA138292, R37CA262209, R01CA238705 and R01CA262555, the Department of Defense Kidney Cancer Research Program under award number W81XWH2210733 and the American Cancer Society. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.