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

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

Research output: Contribution to journalArticlepeer-review

178 Scopus citations

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.

Original languageEnglish
Pages (from-to)115-125
Number of pages11
JournalEuropean Journal of Cancer
Volume94
DOIs
StatePublished - May 2018

Keywords

  • Advanced renal cell carcinoma
  • Cabozantinib
  • First-line
  • IMDC risk groups
  • Sunitinib

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