Safety of pazopanib and sunitinib in treatment-naive patients with metastatic renal cell carcinoma: Asian versus non-Asian subgroup analysis of the COMPARZ trial Journal Article
| Authors: | Guo, J.; Jin, J.; Oya, M.; Uemura, H.; Takahashi, S.; Tatsugami, K.; Rha, S. Y.; Lee, J. L.; Chung, J.; Lim, H. Y.; Wu, H. C.; Chang, Y. H.; Azad, A.; Davis, I. D.; Carrasco-Alfonso, M. J.; Nanua, B.; Han, J.; Ahmad, Q.; Motzer, R. |
| Article Title: | 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 © 2018 The Author(s). |
| Keywords: | adult; controlled study; human tissue; aged; human cell; major clinical study; constipation; fatigue; neutropenia; sunitinib; diarrhea; drug safety; drug withdrawal; hypertension; side effect; treatment duration; liver dysfunction; multiple cycle treatment; anemia; blood toxicity; leukopenia; nausea; randomized controlled trial; stomatitis; thrombocytopenia; dehydration; creatinine; creatinine blood level; renal cell carcinoma; dyspnea; fever; gamma glutamyl transferase blood level; hair color; alanine aminotransferase; aspartate aminotransferase; bilirubin; cause of death; gastrointestinal toxicity; disease severity; heart failure; pazopanib; open study; lactate dehydrogenase; skin discoloration; pancytopenia; headache; phase 3 clinical trial; hypothyroidism; gamma glutamyltransferase; hand foot syndrome; race difference; kidney metastasis; bilirubin blood level; brain hemorrhage; lactate dehydrogenase blood level; proteinuria; tumor bleeding; hematologic disease; drug exposure; caucasian; parallel design; thyrotropin; dysgeusia; respiratory failure; asian; hemoglobinopathy; thyrotropin blood level; hypertransaminasemia; septic shock; european; east asian; south asian; human; male; female; article; japanese (people); alanine aminotransferase level; aspartate aminotransferase level; central asian; north african; palmarplantar erythrodysesthesia; southeast asian |
| Journal Title: | Journal of Hematology & Oncology |
| Volume: | 11 |
| ISSN: | 1756-8722 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2018-05-22 |
| Start Page: | 69 |
| Language: | English |
| DOI: | 10.1186/s13045-018-0617-1 |
| PROVIDER: | scopus |
| PMCID: | PMC5964681 |
| PUBMED: | 29788981 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 July 2018 -- Source: Scopus |
