While metastatic renal cell carcinoma (RCC) has a five-year survival rate of only 10%, patients whose tumors have variant histology or sarcomatoid differentiation face an even more dismal outlook, with limited treatment options. In a study now published in the Journal of Clinical Oncology, a team of researchers led by Bradley McGregor, MD, and Toni Choueiri, MD, reported that atezolizumab in combination with bevacizumab significantly increased progression-free survival and improved outcomes in patients with advanced RCC with variant histology or ≥20% sarcomatoid differentiation. In this interview with i3 Health, Dr. McGregor and Dr. Choueiri, both of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, discuss the promising benefits of atezolizumab/bevacizumab and the future of treatment for patients with this disease.
What are some of the most challenging aspects of treating patients with advanced RCC with variant histology or ≥20% sarcomatoid differentiation?
Bradley McGregor, MD, and Toni Choueiri, MD: Patients with variant histology RCC face a worse prognosis than their counterparts with clear cell RCC. While there have been a number of trials advancing the treatment of clear cell RCC, patients with variant histology were excluded from those trials. Regarding those with sarcomatoid differentiation, these patients often do worse than those without this feature do.
Can you comment on the significance of your results?
Dr. McGregor and Dr. Choueiri: This is the first trial exploring vascular endothelial growth factor (VEGF) inhibitors and immunotherapy combination in RCC with variant histology. Atezolizumab/bevacizumab achieved a response rate of 33% in the overall study population, 50% in patients with clear cell RCC with sarcomatoid differentiation, and 26% in patients with variant histology RCC. Responses were seen independent of histology. The response in patients with clear cell RCC with sarcomatoid differentiation is similar to what has been reported in subgroup analyses of the phase 3 trial IMmotion 151.
What research advances are on the horizon for the treatment of patients with RCC with variant histology or ≥20% sarcomatoid differentiation?
Dr. McGregor and Dr. Choueiri: Patients with clear cell RCC with sarcomatoid differentiation respond well to immunotherapy, which is now a standard of care in the front-line setting: either nivolumab/ipilimumab, which has a response rate approaching 60%, or immunotherapy in combination with VEGF inhibitors. While the combination of atezolizumab and bevacizumab is not approved by regulatory agencies, our data largely supports the role of immunotherapy in combination with VEGF inhibition for these patients. Ongoing studies are exploring the combination of cabozantinib and nivolumab, and studies exploring the addition of cabozantinib to nivolumab/ipilimumab are soon to open.
Do you have any words of advice for community oncologists and other members of the cancer care team as they treat patients with advanced RCC with variant histology or ≥20% sarcomatoid differentiation?
Dr. McGregor and Dr. Choueiri: The best option for these patients is to enroll them in a clinical trial, and if possible, to refer them to a large medical center for evaluation so that we can continue to advance treatment options for this unmet need. This is a heterogeneous group of diseases, and even with our data, there may be some patients, such as those with renal medullary carcinoma, who are best suited to cytotoxic chemotherapy. For patients with clear cell RCC with sarcomatoid differentiation, the best course of action is to pursue an immunotherapy-based regimen in the front-line setting.
For More Information
McGregor BA, McKay RR, Braun DA, et al (2019). Results of a multicenter phase II study of atezolizumab and bevacizumab for patients with metastatic renal cell carcinoma with variant histology and/or sarcomatoid features. J Clin Oncol. [Epub ahead of print] DOI:10.1200/JCO.19.01882
About Dr. McGregor and Dr. Choueiri
Bradley McGregor, MD, is the Clinical Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and an Instructor of Medicine at Harvard Medical School. He specializes in the treatment of genitourinary malignancies and has served as the primary investigator for numerous clinical trials researching novel therapies, especially immunotherapies, and biomarkers for patients with genitourinary malignancies.
Toni Choueiri, MD, is the Director of the Lank Center for Genitourinary Oncology and Co-Leader of the Kidney Cancer Program at the Dana-Farber Cancer Institute. He is also the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School and the former President of Medical Staff at Dana-Farber. Dr. Choueiri specializes in the treatment of genitourinary cancers. His research focuses on the development of novel therapies for genitourinary malignancies, including kidney cancer.
Transcript edited for clarity. Any views expressed above are the speakers' own and do not necessarily reflect those of i3 Health.