ASCO GU 2021: Efficacy of Cabozantinib in Advanced MiT Family Translocation Renal Cell Carcinomas

( MiT family translocation renal cell carcinomas represent a rare (1-5%) and aggressive subgroup of renal cell carcinoma (RCC) harboring high expression of c-MET. Additionally, these tumors are characterized by chromosomal translocations involving TFE3 and TFEB transcription factor genes. Currently, there are no standard treatments for these patients according to the National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines. For advanced disease, median progression-free survival with VEGF-targeted therapy in first-line varies between 3-8.4 months. While response rates of VEGF receptor tyrosine kinase inhibitor and immune checkpoint inhibitors are limited, the efficacy of cabozantinib (a tyrosine kinase inhibitor [TKI] that inhibits VEGFR, MET, and AXL) in this subgroup is unclear. At the the 2021 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium, Dr. Jonathan Thouvenin and colleagues presented results of their study evaluating the efficacy of cabozantinib in advanced MiT family translocation renal cell carcinoma.

This study was a multicenter, retrospective, international cohort study of patients with translocation renal cell carcinoma treated with cabozantinib regardless of the line of treatment at seven centers (three in France and four in the US). The key inclusion criteria included translocation renal cell carcinoma as assessed by a dedicated pathologist, measurable disease, and cabozantinib at any line of therapy. The main objectives were to estimate response rate according to RECIST criteria and to analyze progression-free survival and overall survival.

Among 31 metastatic patients treated in the participating centers, 24 were evaluable for response and were included in this study. This included 21 patients with TFE3 and 3 with TFEB translocations. The median age at diagnosis was 43.5 years (range, 22–70), and the most frequent metastatic sites at diagnosis were lungs (62.5%), retroperitoneal lymph nodes (45.8%), and bone (37.5%). Patients' International Metastatic RCC Database Consortium (IMDC) risk group at diagnosis was favorable in 20.8% of patients, intermediate in 62.5%, and poor-risk in 16.7% of patients. Seven (29%) patients received cabozantinib at first-line treatment, nine (37.5%) at second-line, and eight (33%) at third-line and beyond. The proportion of patients who achieved an objective response was 16.7%, including one complete response and three partial responses. For 11 (45.8%) patients, stable disease was the best response. Over a median follow-up of 14 months (IQR 5-23), the median progression-free survival was 8.4 months (95% confidence interval [CI] 3.6-11.6) and median overall survival was 17 months (95% CI 10.4-not reached [NR]):

PFS and OS in patients with translocation renal cell carcinoma treated with cabozantinib

There was no progression-free survival difference detected overall or in any subgroup except in patients with bone metastasis which harbored a median progression-free survival of 3.6 months as compared to 9.1 months for those without (p=0.03).

Dr. Thouvenin concluded his presentation noting the following summary points:

  • This real-world study provides evidence supporting the activity of cabozantinib in translocation renal cell carcinoma, with more durable responses to therapy than those observed with VEGF receptor tyrosine kinase inhibitor and immune checkpoint inhibitors
  • International collaborations and prospective studies are necessary to identify efficacious therapies for this rare disease that lacks evidence-based treatment options
  • The role of MET expression as a biomarker of response requires investigation
Presented by: Jonathan Thouvenin, MD, Institut de CancĂ©rologie Strasbourg Europe, Strasbourg, France

Written by: Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021
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