HHS Public Access Author manuscript Author Manuscript
Eur Urol. Author manuscript; available in PMC 2017 February 01. Published in final edited form as: Eur Urol. 2016 February ; 69(2): 345–351. doi:10.1016/j.eururo.2015.07.006.
Long-term Safety of Sunitinib in Metastatic Renal Cell Carcinoma Camillo Portaa,*, Martin E. Goreb, Brian I. Rinic, Bernard Escudierd, Subramanian Hariharane, Lorna P. Charlese,†, Liqiang Yange, Liza DeAnnuntise, and Robert J. Motzerf Camillo Porta: [email protected] aIRCCS
Author Manuscript
bRoyal
San Matteo University Hospital Foundation, Pavia, Italy
Marsden Hospital NHS Trust, London, UK
cCleveland dGustave ePfizer
Clinic Taussig Cancer Institute, Cleveland, OH, USA
Roussy, Villejuif, France
Oncology, New York, NY, USA
fMemorial
Sloan-Kettering Cancer Center, New York, NY, USA
Abstract
Author Manuscript
*
Corresponding author. Medical Oncology, IRCCS San Matteo University Hospital Foundation, Piazzale C. Golgi, 19, I-27100 Pavia, Italy. Tel. +39 0382 501355; Fax: +39 0382 502442. †Former Pfizer employee. Author contributions: Camillo Porta had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Porta, Hariharan, Charles, Yang. Acquisition of data: Porta, Gore, Rini, Escudier, Motzer. Analysis and interpretation of data: Porta, Gore, Rini, Escudier, Hariharan, Charles, Yang, DeAnnuntis, Motzer. Drafting of the manuscript: Porta, Gore, Rini, Escudier, Hariharan, Charles, Yang, DeAnnuntis, Motzer. Critical revision of the manuscript for important intellectual content: Porta, Gore, Rini, Escudier, Hariharan, Charles, Yang, DeAnnuntis, Motzer. Statistical analysis: Yang. Obtaining funding: Hariharan, Charles. Administrative, technical, or material support: Yang. Supervision: Hariharan, Charles. Other: None.
Author Manuscript
Financial disclosures: Camillo Porta certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Camillo Porta has received consultancy fees from Pfizer, Bayer Schering Pharma, GlaxoSmithKline, Novartis, BoehringerIngelheim, and AVEO/Astellas; honoraria from Pfizer, Bayer Schering Pharma, GlaxoSmithKline, Novartis, and Astellas; and research funding from Pfizer, Bayer Schering Pharma, and Novartis. Martin E. Gore has received consultancy fees from Pfizer and Astellas and honoraria from Roche, Pfizer, Novartis, and Bristol-Myers Squibb. Brian I. Rini has received research funding and consulting fees from Pfizer. Bernard Escudier has received consultancy fees from Bayer, Pfizer, and Novartis; and honoraria from Bayer, Roche, Pfizer, Genentech, Novartis, and AVEO. Subramanian Hariharan, Liqiang Yang, and Liza DeAnnuntis are full-time employees of Pfizer and hold Pfizer stock. Lorna P. Charles was an employee of Pfizer when these analyses were conducted. Robert J. Motzer has received research funding and consultant fees from Pfizer and has been compensated for expert testimony by Pfizer. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Porta et al.
Page 2
Author Manuscript
Background—Metastatic renal cell carcinoma (mRCC) patients receiving first-line sunitinib typically survive >2 yr, with chronic treatment sometimes extending to ≥6 yr. Objective—To analyze long-term safety with sunitinib in mRCC patients. Design, setting, and participants—Data were pooled from 5739 patients in nine trials, comprising seven phase II studies, a phase III study, and an expanded-access trial in various treatment settings (e.g. cytokine refractory or treatment-naïve). Outcome measurements and statistical analysis—Interval and cumulative time-period analyses evaluated the incidence of treatment-related adverse events (TRAEs) for up to 6 yr, in the overall population and in those with long-term (≥2 yr) sunitinib treatment.
Author Manuscript
Results and limitations—Among long-term patients (n=807), most TRAEs occurred initially in the first year and then decreased in frequency; TRAEs following this pattern included decreased appetite, diarrhea, dysgeusia, dyspepsia, fatigue, hypertension, mucosal inflammation, nausea, and stomatitis. However, hypothyroidism increased by interval analysis from 6% at 0–
Eur Urol. Author manuscript; available in PMC 2017 February 01. Published in final edited form as: Eur Urol. 2016 February ; 69(2): 345–351. doi:10.1016/j.eururo.2015.07.006.
Long-term Safety of Sunitinib in Metastatic Renal Cell Carcinoma Camillo Portaa,*, Martin E. Goreb, Brian I. Rinic, Bernard Escudierd, Subramanian Hariharane, Lorna P. Charlese,†, Liqiang Yange, Liza DeAnnuntise, and Robert J. Motzerf Camillo Porta: [email protected] aIRCCS
Author Manuscript
bRoyal
San Matteo University Hospital Foundation, Pavia, Italy
Marsden Hospital NHS Trust, London, UK
cCleveland dGustave ePfizer
Clinic Taussig Cancer Institute, Cleveland, OH, USA
Roussy, Villejuif, France
Oncology, New York, NY, USA
fMemorial
Sloan-Kettering Cancer Center, New York, NY, USA
Abstract
Author Manuscript
*
Corresponding author. Medical Oncology, IRCCS San Matteo University Hospital Foundation, Piazzale C. Golgi, 19, I-27100 Pavia, Italy. Tel. +39 0382 501355; Fax: +39 0382 502442. †Former Pfizer employee. Author contributions: Camillo Porta had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Porta, Hariharan, Charles, Yang. Acquisition of data: Porta, Gore, Rini, Escudier, Motzer. Analysis and interpretation of data: Porta, Gore, Rini, Escudier, Hariharan, Charles, Yang, DeAnnuntis, Motzer. Drafting of the manuscript: Porta, Gore, Rini, Escudier, Hariharan, Charles, Yang, DeAnnuntis, Motzer. Critical revision of the manuscript for important intellectual content: Porta, Gore, Rini, Escudier, Hariharan, Charles, Yang, DeAnnuntis, Motzer. Statistical analysis: Yang. Obtaining funding: Hariharan, Charles. Administrative, technical, or material support: Yang. Supervision: Hariharan, Charles. Other: None.
Author Manuscript
Financial disclosures: Camillo Porta certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Camillo Porta has received consultancy fees from Pfizer, Bayer Schering Pharma, GlaxoSmithKline, Novartis, BoehringerIngelheim, and AVEO/Astellas; honoraria from Pfizer, Bayer Schering Pharma, GlaxoSmithKline, Novartis, and Astellas; and research funding from Pfizer, Bayer Schering Pharma, and Novartis. Martin E. Gore has received consultancy fees from Pfizer and Astellas and honoraria from Roche, Pfizer, Novartis, and Bristol-Myers Squibb. Brian I. Rini has received research funding and consulting fees from Pfizer. Bernard Escudier has received consultancy fees from Bayer, Pfizer, and Novartis; and honoraria from Bayer, Roche, Pfizer, Genentech, Novartis, and AVEO. Subramanian Hariharan, Liqiang Yang, and Liza DeAnnuntis are full-time employees of Pfizer and hold Pfizer stock. Lorna P. Charles was an employee of Pfizer when these analyses were conducted. Robert J. Motzer has received research funding and consultant fees from Pfizer and has been compensated for expert testimony by Pfizer. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Porta et al.
Page 2
Author Manuscript
Background—Metastatic renal cell carcinoma (mRCC) patients receiving first-line sunitinib typically survive >2 yr, with chronic treatment sometimes extending to ≥6 yr. Objective—To analyze long-term safety with sunitinib in mRCC patients. Design, setting, and participants—Data were pooled from 5739 patients in nine trials, comprising seven phase II studies, a phase III study, and an expanded-access trial in various treatment settings (e.g. cytokine refractory or treatment-naïve). Outcome measurements and statistical analysis—Interval and cumulative time-period analyses evaluated the incidence of treatment-related adverse events (TRAEs) for up to 6 yr, in the overall population and in those with long-term (≥2 yr) sunitinib treatment.
Author Manuscript
Results and limitations—Among long-term patients (n=807), most TRAEs occurred initially in the first year and then decreased in frequency; TRAEs following this pattern included decreased appetite, diarrhea, dysgeusia, dyspepsia, fatigue, hypertension, mucosal inflammation, nausea, and stomatitis. However, hypothyroidism increased by interval analysis from 6% at 0–
