18 A summary from the article by Toni K. Choueiri, Colin Hessel, Susan Halabi, Ben Sanford, M. Dror Michaelson, Olwen Hahn, Meghara Walsh, Thomas Olencki, Joel Picus, Eric J. Small, Shaker Dakhil, Darren R. Feldman, Milan Mangeshkar, Christian Scheffold, Daniel George, Michael J. Morris. Published in European Journal of Cancer 94 (2018) 115-125 Introduction Advanced renal cell carcinoma (RCC) remains incurable despite various treatment options. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria classify patients into prognostic groups based on risk factors, with intermediate and poor-risk patients (70-80% of advanced RCC cases) having shorter survival durations and a greater need for effective therapies. VEGFRtargeted therapies, such as sunitinib and pazopanib, are the current standard rst-line treatments, but progression typically occurs within 8-11 months for mixed-risk populations and less than 6 months for intermediate and poor-risk patients. Targeting additional oncogenic pathways like MET and AXL, which are associated with tumour progression and resistance to VEGF inhibition, may offer therapeutic benets. Cabozantinib, an oral inhibitor of MET, AXL, and VEGFR2, has shown promise in treating advanced RCC after prior antiangiogenic therapy. The CABOSUN trial was designed to compare cabozantinib and sunitinib as initial therapies for metastatic RCC in intermediate or poor-risk patients. Methods The CABOSUN trial was a randomized, phase 2 study conducted at 77 centres in the U.S. to compare cabozantinib and sunitinib as initial therapies for advanced renal cell carcinoma (RCC) in intermediate or poor-risk patients. Eligible participants were 18 years or older, had advanced RCC with a clear-cell component, measurable disease, and no prior systemic treatment. Patients were stratied by IMDC risk group and presence of bone metastases and randomized 1:1 to receive cabozantinib (60 mg daily) or sunitinib (50 mg daily, 4 weeks on/2 weeks off). Treatment continued until disease progression, intolerance, or withdrawal of consent. Tumour response and progression were assessed using RECIST criteria, with radiographic images reviewed by both investigators and a blinded independent radiology review committee (IRC). Outcomes The primary end-point was progression-free survival (PFS). Secondary end-points were objective response rate (ORR), overall survival (OS), and safety. C abozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression-free survival by independent review and overall survival update
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