Pazopanib in the treatment of advanced renal cell carcinoma

Abstract

Pazopanib is an orally available multitargeted tyrosine kinase inhibitor (a class of targeted therapies) that inhibits tumor angiogenesis and cell proliferation. The safety and efficacy of pazopanib (noninferior to sunitinib for progression-free survival) in patients with advanced or metastatic renal cell carcinoma (mRCC) have been demonstrated in several clinical trials. However, in addition to therapeutic efficacy, treatment choices should also take into account health-related quality of life (HRQoL) aspects of cancer therapy. Here, we summarize the HRQoL findings related to pazopanib use, based on patient-reported outcome measures; pazopanib has been shown to be superior to sunitinib on several HRQoL domains (including patient preference). A further consideration for treatment choice is how well the findings from clinical trials correlate with evidence from general clinical practice. This review therefore includes descriptions of real-world experience of pazopanib use in the treatment of patients with mRCC, following its approval by medical regulatory authorities in a number of countries. Naturalistic observational studies demonstrate that the efficacy of pazopanib in patients with mRCC is consistent with clinical trial findings. Similarly, consistent results were observed for the safety profile of pazopanib between observational studies and clinical trials, with most treatment-associated adverse events being mild to moderate in severity, and manageable.

Safety and efficacy of nivolumab in combination with sunitinib or pazopanib in advanced or metastatic renal cell carcinoma: the CheckMate 016 study

“…In second-line trials of sunitinib in aRCC (post VEGF-targeted therapy), reported ORRs have ranged from 15 to 27%, and median PFS has ranged from ~ 5–18 months [ 14 ]. The TKI pazopanib has also demonstrated efficacy in treating first- and second-line aRCC [ 15 ]. In a phase III study (VEG105192) of pazopanib versus placebo in treatment-naïve or pretreated patients ( N = 435), median PFS was 9.2 versus 4.2 months ( P < 0.0001), and ORR was 30% versus 3% ( P < 0.001) [ 11 ].…”

Quality of life in patients with advanced renal cell carcinoma given nivolumab versus everolimus in CheckMate 025: a randomised, open-label, phase 3 trial

“…3,17–19 In patients receiving first-line therapy with pazopanib, or second-line and subsequent therapy with axitinib, sorafenib, pazopanib, and everolimus, HRQoL was maintained but not improved when compared with placebo. 3,5,18,20 In the CheckMate 025 trial, the deterioration in HRQoL in patients treated with everolimus may reflect toxicities associated with this agent. 21 Consequently, the improvements in HRQoL with nivolumab treatment compared with everolimus treatment in the CheckMate 025 trial are particularly noteworthy.…”

“…1,2 Anti-angiogenic and mTOR-targeted agents have changed the therapeutic landscape for advanced or metastatic RCC (aRCC), but these treatments are associated with limited overall survival (OS), toxicities related to their specific mechanisms of action, and limited improvement in health-related quality of life (HRQoL) for this patient population. 1,3–5 …”

Pazopanib: Evidence review and clinical practice in the management of advanced renal cell carcinoma

“…This evidence is consistent with that obtained in a retrospective comparative study [ 25 , 26 ] (Table 2 ) and also in the real-life retrospective SPAZO study [ 25 , 26 ] which showed a PFS of 11.1 months. Other studies have reported PFS rates of between 10.5 and 14.1 months [ 19 , 27 – 29 ].…”