Safety of pazopanib and sunitinib in treatment-naive patients with metastatic renal cell carcinoma: Asian versus non-Asian subgroup analysis of the COMPARZ trial

Abstract

Background: The international, phase 3 COMPARZ study demonstrated that pazopanib and sunitinib have comparable efficacy as first-line therapy in patients with advanced renal cell carcinoma, but that safety and quality-of-life profiles favor pazopanib. Our report analyzed pazopanib and sunitinib safety in Asian and non-Asian subpopulations.

Methods: Patients were randomized 1:1 to receive pazopanib 800 mg once daily (continuous dosing) or sunitinib 50 mg once daily in 6-week cycles (4 weeks on, 2 weeks off).

Results: Safety population was composed of 363 Asian patients and 703 non-Asian patients. Asian patients had similar duration of exposure to either drug compared with non-Asian patients, although Asian patients had a higher frequency of dose modifications. Overall, hematologic toxicities, cytopenias, increased AST/ALT, and palmar-plantar erythrodysesthesia (PPE) were more prevalent in Asian patients, whereas gastrointestinal toxicities were more prevalent in non-Asian patients. Among Asian patients, hematologic adverse events and most non-hematologic AEs were more common in sunitinib-treated versus pazopanib-treated patients. Among Asian patients, the most common grade 3/4 AEs with pazopanib were hypertension (grade 3, 22%) and alanine aminotransferase increased (grade 3, 12%; grade 4, 1%); the most common grade 3/4 AEs with sunitinib were thrombocytopenia/platelet count decreased (grade 3, 36%; grade 4, 10%), neutropenia/neutrophil count decreased (grade 3, 24%; grade 4, 3%) hypertension (grade 3, 20%), and PPE (grade 3, 15%).

Conclusions: A distinct pattern and severity of adverse events was observed in Asians when compared with non-Asians with both pazopanib and sunitinib. However, the two drugs were well tolerated in both subpopulations.

Trial registration: ClinicalTrials.gov, NCT00720941 , Registered July 22, 2008 ClinicalTrials.gov, NCT01147822 , Registered June 22, 2010.

Keywords: Pazopanib; Renal cell carcinoma; Sunitinib.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the institutional review board or ethics committee at each participating center and was conducted in accordance with the provisions of the Declaration of Helsinki and Good Clinical Practice guidelines. A data and safety monitoring board reviewed safety data during the study. Written informed consent was obtained from each patient prior to participation in the study.

Competing interests

Shunji Takahashi received research funding and honoraria from Novartis Pharmaceuticals Corporation. Arun Azad received consultant, speakers bureau, and honoraria from Novartis Pharmaceuticals Corporation. Hirotsugu Uemura received research funding, speakers bureau, and honoraria from Novartis Pharmaceuticals Corporation and received research funding, speakers bureau, and honoraria from Pfizer. Bhupinder Nanua, Jackie Han, and Qasim Ahmad are employees of Novartis Pharmaceuticals Corporation. Marlene J. Carrasco-Alfonso is an employee and shareholder of Novartis Pharmaceuticals Corporation. Jun Guo, Jie Jin, Mototsugu Oya, Katsunori Tatsugami, Sun Young Rha, Jae-Lyun Lee, Jinsoo Chung, Ho Yeong Lim, Hsi Chin Wu, Yen Hwa Chang, Ian D. Davis, Robert Motzer report no conflicts of interest.

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Figures

Fig. 1

Adverse effects for which a frequency difference of ≥ 10% was observed between Asian and non-Asian populations in COMPARZ. ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; Paz, pazopanib; PPE, palmar-plantar erythrodysesthesia; Sun, sunitinib; WBC, white blood cells