In the APHINITY study (NCT01358877, BIG 4-11/BO25126/TOC4939G), pertuzumab added to trastuzumab and chemotherapy significantly improved invasive disease-free survival as adjuvant treatment for patients with HER2-positive early breast cancer. The objective of this analysis was to assess the pharmacokinetics of pertuzumab in combination with trastuzumab in Chinese patients with early breast cancer. Samples for pertuzumab and trastuzumab pharmacokinetic analysis were taken from Chinese patients during cycle 1 of treatment and at steady-state in cycle 10. Noncompartmental analysis was used to estimate minimum and maximum serum concentrations (Cmax and Cmin), area under the concentration-time curve, clearance, and other pharmacokinetic parameters. In 15 patients, mean steady-state Cmax and Cmin pertuzumab serum concentrations (368 ± 177 μg/ml, and 122 ± 47 μg/ml, respectively) were numerically higher than observed previously in a pharmacokinetic analysis of the global population in APHINITY and in patients treated in the metastatic setting. The geometric mean ratio and corresponding 90% confidence interval for trastuzumab Cmax and Cmin in the presence (n = 15) or absence (n = 17) of pertuzumab were 104.6 (91.09–120) and 98.23 (84.58–114), respectively, indicating no apparent impact of pertuzumab on the pharmacokinetics of trastuzumab. Increases in pertuzumab Cmax and Cmin were not associated with an increase in adverse events. The APHINITY Chinese pharmacokinetic substudy analysis supports the dosing regimen for pertuzumab (840 mg loading dose followed by 420 mg maintenance doses every 3 weeks administered by intravenous infusion) in a Chinese HER2-positive early breast cancer patient population.
aNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing
bThe First Hospital of Jilin University, Changchun
cAcademy of Military Medical Sciences Affiliated Hospital (307 Hospital of PLA), Beijing
dThe Tumor Hospital of Harbin Medical University, Harbin
eShanghai First People’s Hospital, Shanghai
fCurrent affiliation for Liwei Wang is Renji Hospital, Shanghai
gRoche China Holdings, Shanghai
hCurrent affiliation for Yixiang Mao is Oncology Clinical Research, MSD China, Shanghai, China
iMaastricht University Medical Center, Maastricht, Netherlands
jSeoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
kFrontier Science (Scotland) Ltd, Kincraig, Scotland
lBreast International Group, Brussels, Belgium
mNational Cancer Institute, Rio de Janeiro, Brazil
nGenentech, Inc., South San Francisco
oCurrent affiliation for Amit Garg is Seattle Genetics, South San Francisco, California, USA
* Yang Luo and Wei Li are joint first authors.
† Binghe Xu and Whitney P. Kirschbrown are joint corresponding authors.
Received 12 March 2019 Revised form accepted 21 May 2019
Correspondence to Binghe Xu, MD, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China, Tel: +8610 8778 8826; e-mail firstname.lastname@example.org
Correspondence to Whitney P. Kirschbrown, PharmD, PhD, Genentech, Inc., 1 DNA Way, MS463a, South San Francisco, CA 94080, USA, Tel: +1 650 467 3808; e-mail: email@example.com