Angiogenesis inhibitor therapies for advanced renal cell carcinoma: Toxicity and treatment patterns in clinical practice from a global medical chart review

Abstract

The aim of this study was to assess the treatment patterns and safety of sunitinib, sorafenib and bevacizumab in real-world clinical settings in US, Europe and Asia. Medical records were abstracted at 18 community oncology clinics in the US and at 21 tertiary oncology centers in US, Europe and Asia for 883 patients ≥18 years who had histologically/cytologically confirmed diagnosis of advanced RCC and received sunitinib (n=631), sorafenib (n=207) or bevacizumab (n=45) as first-line treatment. No prior treatment was permitted. Data were collected on all adverse events (AEs) and treatment modifications, including discontinuation, interruption and dose reduction. Treatment duration was estimated using Kaplan-Meier analysis. Demographics were similar across treatment groups and regions. Median treatment duration ranged from 6.1 to 10.7 months, 5.1 to 8.5 months and 7.5 to 9.8 months for sunitinib, sorafenib and bevacizumab patients, respectively. Grade 3/4 AEs were experienced by 26.0, 28.0 and 15.6% of sunitinib, sorafenib and bevacizumab patients, respectively. Treatment discontinuations occurred in 62.4 (Asia) to 63.1% (US) sunitinib, 68.8 (Asia) to 90.0% (Europe) sorafenib, and 66.7 (Asia) to 81.8% (US) bevacizumab patients. Globally, treatment modifications due to AEs occurred in 55.1, 54.2 and 50.0% sunitinib, sorafenib and bevacizumab patients, respectively. This study in a large, global cohort of advanced RCC patients found that angiogenesis inhibitors are associated with high rates of AEs and treatment modifications. Findings suggest an unmet need for more tolerable agents for RCC treatment.

Persistence and Compliance Among U.S. Patients Receiving Pazopanib or Sunitinib as First-Line Therapy for Advanced Renal Cell Carcinoma: A Retrospective Claims Analysis

“…36 Factors influencing duration of treatment have not been consistently studied. However, retrospective chart review 33,35 and claims database studies 31,32 have shown that a high proportion (15%-40%) of patients will discontinue, reduce dosage, or switch oral RCC treatments due to adverse events. Thus, studies of compliance and persistence patterns are vitally important.…”

“…34,35 In the clinical trial that demonstrated pazopanib was noninferior to sunitinib with regard to PFS, the median duration of exposure to the study drugs was 8 months for pazopanib and 8 months for sunitinib. 36 Factors influencing duration of treatment have not been consistently studied.…”

Persistence and Compliance with Pazopanib in Patients with Advanced Renal Cell Carcinoma Within a U.S. Administrative Claims Database

“…[21][22][23][24] A retrospective database study of dosing patterns of first-line sunitinib, dosed once daily on a 4-weeks-on, 2-weeks-off dosing schedule, showed that patients commonly underwent sunitinib dose reductions within the first 3 treatment cycles due to toxicity and discontinued therapy within the first 5 cycles due to progressive disease. 25 Combined, the findings from these studies suggest that a high percentage of patients in routine clinical settings could discontinue treatment with TKIs in < 6 months.…”

Sunitinib side effects as surrogate biomarkers of efficacy

“…With more than 10 years of experience with this agent, there is increased understanding of the mechanism-based AEs associated with sunitinib, the most common of which are hypertension, hypothyroidism, hand-foot syndrome, asthenia/fatigue, neutropenia, and thrombocytopenia. These AEs can lead to dose reductions, interruptions, and discontinuations 11 -all of which may negatively impact outcomes in patients with mRCC. However, some, including hypertension, hypothyroidism, hand-foot syndrome, and neutropenia, have been explored as potential biomarkers of the clinical efficacy of sunitinib.…”