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Clinical Trial
. 2018 May:94:115-125.
doi: 10.1016/j.ejca.2018.02.012. Epub 2018 Mar 20.

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  1 , Colin Hessel  2 , Susan Halabi  3 , Ben Sanford  4 , M Dror Michaelson  5 , Olwen Hahn  6 , Meghara Walsh  7 , Thomas Olencki  8 , Joel Picus  9 , Eric J Small  10 , Shaker Dakhil  11 , Darren R Feldman  12 , Milan Mangeshkar  2 , Christian Scheffold  2 , Daniel George  13 , Michael J Morris  12
Affiliations
Clinical Trial

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 et al. Eur J Cancer. 2018 May.

Erratum in

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.

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Figures

Fig. 1.
Fig. 1.. Trial profile through September 15, 2016.
PFS, progression-free survival.
Fig. 2.
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.
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.
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.
See this image and copyright information in PMC

References

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