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, 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

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.

Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1.. Trial profile through September 15,…
Fig. 1.. Trial profile through September 15, 2016.
PFS, progression-free survival.
Fig. 2.. Kaplan—Meier plot of progression-free survival…
Fig. 2.. Kaplan—Meier plot of progression-free survival per independent radiology review committee through September 15, 2016.
All 157 randomised patients were included in the analysis. HR, hazard ratio; PFS, progression-free survival.
Fig. 3.. Best target lesion change from…
Fig. 3.. Best target lesion change from baseline
*Confirmed partial responses. Six patients in the cabozantinib group and 18 patients in the sunitinib group were unevaluable because they had no adequate post-baseline imaging assessments (Table 2).
Fig. 4.. Kaplan—Meier plot of overall survival…
Fig. 4.. Kaplan—Meier plot of overall survival through July 01, 2017.
All 157 randomised patients were included in the analysis. HR, hazard ratio; OS, overall survival.

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