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

Jun Guo, Jie Jin, Mototsugu Oya, Hirotsugu Uemura, Shunji Takahashi, Katsunori Tatsugami, Sun Young Rha, Jae Lyun Lee, Jinsoo Chung, Ho Yeong Lim, Hsi Chin Wu, Yen Hwa Chang, Arun Azad, Ian D. Davis, Marlene J. Carrasco-Alfonso, Bhupinder Nanua, Jackie Han, Qasim Ahmad, Robert Motzer

Research output: Contribution to journalArticleResearchpeer-review

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

Original languageEnglish
Article number69
Number of pages10
JournalJournal of Hematology & Oncology
Volume11
Issue number1
DOIs
Publication statusPublished - 22 May 2018

Keywords

  • Pazopanib
  • Renal cell carcinoma
  • Sunitinib

Cite this

Guo, Jun ; Jin, Jie ; Oya, Mototsugu ; Uemura, Hirotsugu ; Takahashi, Shunji ; Tatsugami, Katsunori ; Rha, Sun Young ; Lee, Jae Lyun ; Chung, Jinsoo ; Lim, Ho Yeong ; Wu, Hsi Chin ; Chang, Yen Hwa ; Azad, Arun ; Davis, Ian D. ; Carrasco-Alfonso, Marlene J. ; Nanua, Bhupinder ; Han, Jackie ; Ahmad, Qasim ; Motzer, Robert. / Safety of pazopanib and sunitinib in treatment-naive patients with metastatic renal cell carcinoma : Asian versus non-Asian subgroup analysis of the COMPARZ trial. In: Journal of Hematology & Oncology. 2018 ; Vol. 11, No. 1.
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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",
keywords = "Pazopanib, Renal cell carcinoma, Sunitinib",
author = "Jun Guo and Jie Jin and Mototsugu Oya and Hirotsugu Uemura and Shunji Takahashi and Katsunori Tatsugami and Rha, {Sun Young} and Lee, {Jae Lyun} and Jinsoo Chung and Lim, {Ho Yeong} and Wu, {Hsi Chin} and Chang, {Yen Hwa} and Arun Azad and Davis, {Ian D.} and Carrasco-Alfonso, {Marlene J.} and Bhupinder Nanua and Jackie Han and Qasim Ahmad and Robert Motzer",
year = "2018",
month = "5",
day = "22",
doi = "10.1186/s13045-018-0617-1",
language = "English",
volume = "11",
journal = "Journal of Hematology & Oncology",
issn = "1756-8722",
publisher = "Springer-Verlag London Ltd.",
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Guo, J, Jin, J, Oya, M, Uemura, H, Takahashi, S, Tatsugami, K, Rha, SY, Lee, JL, Chung, J, Lim, HY, Wu, HC, Chang, YH, Azad, A, Davis, ID, Carrasco-Alfonso, MJ, Nanua, B, Han, J, Ahmad, Q & Motzer, R 2018, '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 of Hematology & Oncology, vol. 11, no. 1, 69. https://doi.org/10.1186/s13045-018-0617-1

Safety of pazopanib and sunitinib in treatment-naive patients with metastatic renal cell carcinoma : Asian versus non-Asian subgroup analysis of the COMPARZ trial. / Guo, Jun; Jin, Jie; Oya, Mototsugu; Uemura, Hirotsugu; Takahashi, Shunji; Tatsugami, Katsunori; Rha, Sun Young; Lee, Jae Lyun; Chung, Jinsoo; Lim, Ho Yeong; Wu, Hsi Chin; Chang, Yen Hwa; Azad, Arun; Davis, Ian D.; Carrasco-Alfonso, Marlene J.; Nanua, Bhupinder; Han, Jackie; Ahmad, Qasim; Motzer, Robert.

In: Journal of Hematology & Oncology, Vol. 11, No. 1, 69, 22.05.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Safety of pazopanib and sunitinib in treatment-naive patients with metastatic renal cell carcinoma

T2 - Asian versus non-Asian subgroup analysis of the COMPARZ trial

AU - Guo, Jun

AU - Jin, Jie

AU - Oya, Mototsugu

AU - Uemura, Hirotsugu

AU - Takahashi, Shunji

AU - Tatsugami, Katsunori

AU - Rha, Sun Young

AU - Lee, Jae Lyun

AU - Chung, Jinsoo

AU - Lim, Ho Yeong

AU - Wu, Hsi Chin

AU - Chang, Yen Hwa

AU - Azad, Arun

AU - Davis, Ian D.

AU - Carrasco-Alfonso, Marlene J.

AU - Nanua, Bhupinder

AU - Han, Jackie

AU - Ahmad, Qasim

AU - Motzer, Robert

PY - 2018/5/22

Y1 - 2018/5/22

N2 - 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

AB - 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

KW - Pazopanib

KW - Renal cell carcinoma

KW - Sunitinib

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