@article{6d7a95b7e0db4a6180a505b0c0677131,
title = "Cabozantinib 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",
abstract = "Background: The randomised phase 2 CABOSUN trial comparing cabozantinib with sunitinib as initial therapy for advanced renal cell carcinoma (RCC) of intermediate or poor risk met the primary end-point of improving progression-free survival (PFS) as assessed by investigator. We report PFS by independent radiology review committee (IRC) assessment, ORR per IRC and updated overall survival (OS). Patients and methods: Previously untreated patients with advanced RCC of intermediate or poor risk by IMDC criteria were randomised 1:1 to cabozantinib 60 mg daily or sunitinib 50 mg daily (4 weeks on/2 weeks off). Stratification was by risk group and presence of bone metastases. Results: A total of 157 patients were randomised 1:1 to cabozantinib (n = 79) or sunitinib (n = 78). Median PFS per IRC was 8.6 months (95% confidence interval [CI] 6.8–14.0) versus 5.3 months (95% CI 3.0–8.2) for cabozantinib versus sunitinib (hazard ratio [HR] 0.48 [95% CI 0.31–0.74]; two-sided p = 0.0008), and ORR per IRC was 20% (95% CI 12.0–30.8) versus 9% (95% CI 3.7–17.6), respectively. Subgroup analyses of PFS by stratification factors and MET tumour expression were consistent with results for the overall population. With a median follow-up of 34.5 months, median OS was 26.6 months (95% CI 14.6–not estimable) with cabozantinib and 21.2 months (95% CI 16.3–27.4) with sunitinib (HR 0.80 [95% CI 0.53–1.21]. The incidence of grade 3 or 4 adverse events was 68% for cabozantinib and 65% for sunitinib. Conclusions: In this phase 2 trial, cabozantinib treatment significantly prolonged PFS per IRC compared with sunitinib as initial systemic therapy for advanced RCC of poor or intermediate risk. Trial Registration Number: NCT01835158.",
keywords = "Advanced renal cell carcinoma, Cabozantinib, First-line, IMDC risk groups, Sunitinib",
author = "Choueiri, {Toni K.} and Colin Hessel and Susan Halabi and Ben Sanford and Michaelson, {M. Dror} and Olwen Hahn and Meghara Walsh and Thomas Olencki and Joel Picus and Small, {Eric J.} and Shaker Dakhil and Feldman, {Darren R.} and Milan Mangeshkar and Christian Scheffold and Daniel George and Morris, {Michael J.}",
note = "Funding Information: The authors thank the patients, their families, the investigators and site staff, the Alliance for Clinical Trials in Oncology, the Cancer Therapy Evaluation Program (John Wright), and the study teams participating in this trial. Research reported in this publication was supported by National Institutes of Health (award numbers U10CA180821 and U10CA180882 [to the Alliance for Clinical Trials in Oncology], U10CA180791 , U10CA180833 , U10CA180850 , U10CA180857 , U10CA180867 ) and Exelixis, Inc . The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. TKC is supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE and Program , the Kohlberg Chair at Harvard Medical School and the Trust Family , Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at the Dana-Farber Cancer Institute. Patient treatment at Memorial Sloan Kettering Cancer Center was supported in part by Memorial Sloan Kettering Cancer Center Support Grant/Core Grant ( P30 CA008748 ). Medical writing support was provided by Julie C Lougheed, PhD (Exelixis) with editorial assistance by Fishawack Communications (Conshohocken, PA, USA), which was funded by Exelixis . Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2018",
month = may,
doi = "10.1016/j.ejca.2018.02.012",
language = "English",
volume = "94",
pages = "115--125",
journal = "European Journal of Cancer",
issn = "0959-8049",
}