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

Autor: Darren R. Feldman, Milan Mangeshkar, M. Dror Michaelson, Shaker R. Dakhil, Ben L. Sanford, Daniel J. George, Meghara K. Walsh, Thomas Olencki, Joel Picus, Susan Halabi, Colin Hessel, Toni K. Choueiri, Olwen Hahn, Michael J. Morris, Christian Scheffold, Eric J. Small
Rok vydání: 2017
Předmět:
0301 basic medicine
Oncology
Male
Cancer Research
medicine.medical_specialty
Cabozantinib
Pyridines
Population
Antineoplastic Agents
Kaplan-Meier Estimate
Advanced renal cell carcinoma
urologic and male genital diseases
Article
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Renal cell carcinoma
Internal medicine
Sunitinib
Medicine
Humans
Anilides
Progression-free survival
Adverse effect
education
Carcinoma
Renal Cell
Aged
Proportional Hazards Models
education.field_of_study
business.industry
Hazard ratio
First-line
Middle Aged
medicine.disease
female genital diseases and pregnancy complications
Confidence interval
Kidney Neoplasms
Progression-Free Survival
3. Good health
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Female
business
IMDC risk groups
medicine.drug
Zdroj: European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Popis: 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 .
Databáze: OpenAIRE
Externí odkaz: