Sequential Treatment with Pazopanib and Everolimus in Metastatic Renal Cell Carcinoma

Abstract

In metastatic renal cell carcinoma, complete response to first-line antiangiogenic agents is rare and resistance to therapy often develops. Protocols for sequential treatment with angiogenesis and mTOR inhibitors are under evaluation to improve outcomes. In this observational, real-world study, patients received a first-line therapy with pazopanib until discontinuation for disease progression or toxicity, then a second-line with everolimus. Primary endpoints were overall survival (OS) for sequence, progression free survival (PFS) for each agent, and safety. Thirty-one patients were included in the analysis: 73.3% of patients underwent nephrectomy before treatment, 25.8% had at least three comorbidities. At the beginning of therapy, the median age was 68 years, with more than 60% of patients older than 65 years. The median OS for sequence was 26.5 months (95% CI 17.4-nc); median PFS was 10.6 months (95% CI 6.3–12.1) with pazopanib and 5.3 months (95% CI 3.8–6.7) with everolimus. The median persistence in pazopanib therapy was 8.1 months (Interquartile Range IQR 5.3–12.7), with 31% of patients who required dose reduction, while persistence in everolimus was 4.4 months (IQR 3.4–6.5). Sequence was well tolerated with a different profile of adverse events for each agent. These data confirmed that pazopanib was effective, even in reduced dosing, and well tolerated and suggested that everolimus may represent an opportunity to continue a therapy when patients cannot further tolerate angiogenesis inhibitors or develop a resistance.

Pazopanib as salvage therapy in metastatic renal cell carcinoma with hypercalcemic crisis and renal insufficiency: a case report and literature review

“…In a global, randomized, double-blind, placebo-controlled phase III study of the 435 treatment-naive and cytokine-pretreated patients with advanced RCC, pazopanib improved PFS when compared with placebo (median, 9.2 vs. 4.2 months; hazard ratio, 0.46) ( 10 ). In the real-world, median PFS with pazopanib as first-line therapy was 10.6 months (from 5.3 to 13.7 months) ( 11 ). In the subgroup analysis of the COMPARTZ phase 3 randomized trial for 209 Chinese patients, the PFS was 8.0 months, and the objective response rate (ORR) was 35% ( 12 ).…”

A network meta-analysis of short-term efficacy of different single-drug targeted therapies in the treatment of renal cell carcinoma

“…A previous study has shown that targeted therapies act by blocking essential biochemical pathways or mutant proteins that are required for tumor cell growth and survival and the ability to inhibit the tumor cell growth and survival may explain the different efficacy of different single-drug targeted therapies for RCC [ 50 ]. Rossetti et al [ 51 ] confirmed that Pazopanib was effective, even in reduced dosing, and well tolerated and suggested that Everolimus may represent an opportunity to continue a therapy when patients cannot further tolerate angiogenesis inhibitors or develop a resistance. Recently, two randomized Phase III trials (METEOR and CheckMate 025) demonstrated the inferiority of Everolimus in second-line setting compared with the TKI Cabozantinib and with the immune checkpoint inhibitor nivolumab respectively [ 52 ].…”