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.

Cabozantinib Versus Sunitinib for Untreated Patients with Advanced Renal Cell Carcinoma of Intermediate or Poor Risk: Subgroup Analysis of the Alliance A031203 CABOSUN trial

“…The CABOSUN trial and retrospective analysis of PFS and ORR by IRC have been previously described . Eligible patients were ≥18 years of age with advanced or metastatic clear‐cell RCC without previous systemic treatment.…”

“…Cabozantinib is an oral inhibitor of MET, AXL, and vascular endothelial growth factor (VEGF) receptors . The phase II CABOSUN trial (Alliance for Clinical Trials in Oncology A031203) compared cabozantinib with sunitinib as initial treatment in patients with advanced renal cell carcinoma (RCC) of intermediate or poor International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk . The study met the primary endpoint of improved progression‐free survival (PFS) per investigator with cabozantinib versus sunitinib.…”

Vascular endothelial growth factor and programmed death‐1 pathway inhibitors in renal cell carcinoma

“…Cabozantinib improved median PFS to 8.2 months compared with 5.6 months for sunitinib in the first‐line setting (HR, 0.66; 95% CI, 0.46‐0.95; 1‐sided P = .12) . OS was 26.6 months with cabozantinib and 21.2 months with sunitinib (HR, 0.80; 95% CI, 0.53‐1.21) …”

“…Clinical trials cannot be directly compared given the differences in patient populations and trial methods. Table shows the ORRs, CR rates, PFS, and OS for the key trials in first‐line and second‐line VEGF inhibitor and ICI monotherapy. There are limited data on the activity of single‐agent PD‐1 inhibitors in the first‐line setting, and phase 3 trials of combination therapy did not use single‐agent ICI as a comparison arm; therefore, it is not known which patients benefit from the combination of nivo/ipi versus anti–PD‐1 monotherapy at this time.…”

Cabozantinib zur Erstlinientherapie des fortgeschrittenen Nierenzellkarzinoms zugelassen. Oraler Tyrosinkinase-Inhibitor zeigt signifikanten klinischen Vorteil im PFS

“…Kaplan-Meier-Kurve des progressionsfreien Überlebens (PFS) bis 15. September 2016 nach Analyse des IRC, modifiziert nach [7].…”