First-line sunitinib or pazopanib in metastatic renal cell carcinoma: The Canadian experience

Abstract

Introduction: Clinical trial data has shown pazopanib to be noninferior in overall survival (OS) compared to sunitinib as first-line treatment for metastatic renal cell carcinoma (mRCC). The purpose of this study was to evaluate outcomes and compare dose-modifying toxicities of mRCC patients treated with suntinib or pazopanib in the real-world setting. Methods: Data were collected on mRCC patients using the prospective Canadian Kidney Cancer Information System (CKCis) database from January 2011 to November 2015. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan-Meier method. Results: We identified 670 patients treated with sunitinib (n=577) and pazopanib (n=93). There were no significant differences in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (p=0.807). Patients treated with sunitinib had improved OS compared with pazopanib (median 31.7 vs. 20.6 months, p=0.028; adjusted hazard ratio [aHR] 0.60; 95% confidence interval [CI] 0.38-0.94). Time to treatment failure (TTF) was numerically, but not statistically, improved with sunitinib (medians 11.0 vs. 8.4 months, p=0.130; aHR 0.87; 95% CI 0.59-1.28). Outcomes with individualized dosing on sunitinib were unavailable for this analysis. Patients treated with sunitinib had a higher incidence of mucositis, hand-foot syndrome, and gastroesophageal reflux disease; patients treated with pazopanib had a higher incidence of hepatotoxicity. Conclusions: In Canadian patients with mRCC, treatment with sunitinib appears to be associated with an improved OS compared to pazopanib in the first-line setting. Patient selection factors and the contemporary practice of individualized dosing with sunitinib may contribute to these real-world outcomes and warrant further investigation.

The Current and Evolving Landscape of First-Line Treatments for Advanced Renal Cell Carcinoma

“…The efficacy and safety of sunitinib in treatment-naive patients with advanced clear cell RCC was demonstrated in the pivotal phase III trial, in which sunitinib significantly prolonged median progression-free survival (mPFS) but not overall survival (OS) versus IFN-α [17, 18] ( Table 1). Several real-world studies confirm the effectiveness of first-line sunitinib in patients with aRCC [19][20][21][22][23][24][25][26][27][28][29][30]. Most large (n > 150) real-world studies are retrospective, multicenter analyses with a wide range in mPFS (7.0-20.0 months) and median OS (mOS; 18.7-45.1 months) reported across studies [19][20][21][22][23][24][25][26][27][28][29][30].…”

“…Several real-world studies confirm the effectiveness of first-line sunitinib in patients with aRCC [19][20][21][22][23][24][25][26][27][28][29][30]. Most large (n > 150) real-world studies are retrospective, multicenter analyses with a wide range in mPFS (7.0-20.0 months) and median OS (mOS; 18.7-45.1 months) reported across studies [19][20][21][22][23][24][25][26][27][28][29][30]. In one of the larger realworld sunitinib studies that provided information about the effectiveness in patient subgroups often excluded from clinical trials, an expanded-access trial in 4,543 patients with metastatic RCC demonstrated that the objective response rate (ORR) was 16% and mPFS and mOS were 9.4 and 18.7 months, respectively [21].…”

“…Real-world studies confirm the effectiveness and safety of first-line pazopanib in patients with aRCC, [28][29][30][46][47][48][49][50], but these have generally been conducted in older patients with similar survival results when compared with younger patient populations in clinical trials (median age: ≥65 vs. 59-61 years [34,44]). Most completed real-world studies of first-line pazopanib are retrospective, multicenter analyses (n > 80), with a mPFS range of 8.3-13.7 months and mOS range of 19-29.1 months across studies [28][29][30][42][43][44][45][46], consistent with results from phase III trials [34,44,45,51]. The retrospective, observational Spanish SPAZO study in 278 patients with metastatic RCC, which was one of the largest reported real-world studies of first-line pazopanib (mPFS and mOS were 11.1 and 22.2 months, respectively), validated the IMDC criteria widely used for assessing prognosis with first-line anti-VEGF therapy [46].…”

“…Although no OS benefit was observed with pazopanib versus placebo, this was confounded by the early and high rate of crossover from placebo to pazopanib . Real‐world studies confirm the effectiveness and safety of first‐line pazopanib in patients with aRCC, , but these have generally been conducted in older patients with similar survival results when compared with younger patient populations in clinical trials (median age: ≥65 vs. 59–61 years ). Most completed real‐world studies of first‐line pazopanib are retrospective, multicenter analyses ( n > 80), with a mPFS range of 8.3–13.7 months and mOS range of 19–29.1 months across studies , consistent with results from phase III trials .…”

Pazopanib has equivalent anti-tumor effectiveness and lower Total costs than Sunitinib for treating metastatic or advanced renal cell carcinoma: a meta-analysis

“…However, a phase II RCT demonstrated no significant difference in the total number of adverse events (AEs) between the sunitinib and pazopanib groups [8]. Other studies indicated that sunitinib was associated with better OS than pazopanib [9].…”