Pazopanib After ICIs Improves PFS, ORR in Metastatic Renal Cell Carcinoma

Findings from an international, single-arm, phase II trial of the efficacy of pazopanib following immune checkpoint inhibitor (ICI) treatment for patients with metastatic renal cell carcinoma (mRCC), has established that second line pazopanib was associated with longer progression-free survival (PFS) and a higher overall response rates (ORR; Annals of Oncology. 2020;31(suppl_4):S550).

“Immune checkpoint inhibitors are increasingly used in the initial treatment of mRCC. The aim of this study was to evaluate the safety and efficacy of the vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) pazopanib (PAZ) in patients with advanced or mRCC following previous ICI treatment,” wrote Thomas Powles, MD, Medical Oncology, Bart's Cancer Institute, Queen Mary University of London, England and colleagues.

A total of 62 patients previously treated with ICI were enrolled in the study and given 800mg of pazopanib once daily, with treatment only stopping upon the event of disease progression, unacceptable toxicity, death, or study withdrawal.

The primary endpoint was progression-free survival (PFS) based on local investigator assessment. Overall response rates based on local investigator assessment, overall survival (OS), and safety were the secondary endpoints.

Patients received PAZ as 2nd line (2L; n = 47; 25% had prior anti-VEGF therapy) or 3rd line (3L; n = 15, 100% had prior anti-VEGF therapy) treatment for ≥6 treatment cycles.

According to IMDC prognosis at baseline, 32% of patients were favorable, 56.5% intermediate, and 11.3% poor. 

During a median follow-up of 10.2 months, patients receiving 2L PAZ had a median PFS of 7.4 months (95% CI: 3.7, 13.8) and survival probability at 12 months was 65.8. Alternatively, median PFS was 4.6 months (95% CI: 3.3, 9.2) in the 3L setting, and survival probability at 12 months was 75.8% (95% CI: 40.4%, 91.9%). The ORR in the 2L and 3L settings was 19% and 0% respectively.

Treatment-related adverse events (AEs) included diarrhea (40%), liver abnormalities (34%), fatigue (31%), decreased appetite (26%), and nausea (24%). Furthermore, 31% of patients reported AEs leading to treatment withdrawal, with 16% of those due to liver abnormalities; 71% of patients experienced AEs which required dose adjustment or interruptions. Transaminase elevations of grade 3/4 occurred in 24.2% of patients, but there were no related deaths.

“PAZ has activity after progression on ICIs in mRCC. AE profiles are in line with the expectations for this TKI,” concluded Dr Powles et al.—Alexandra Graziano