Oncology Therapy Drugs in China, Japan, and the United States: Pharmacokinetic Characteristics, Dose Regimens, and Development Strategies

Zhou, Li; Higashimori, Mitsuo; Shen, Kaikai; Zhang, Zhenxian; Sheng, Jennifer; Xu, Hongmei; Horiuchi, Masato; Ichikawa, Keita; Al‐Huniti, Nidal; Zhou, Diansong

doi:10.1002/cpt.1352

Cited by 9 publications

(7 citation statements)

References 6 publications

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“…This was consistent with previous reports. 6 , 7 , 8 , 9 We also echo the previous reports 2 , 3 , 10 that PK of mAbs are similar in Japanese and non‐Japanese. In general, mAbs are not widely distributed to organs/tissues, and elimination is not related to the expression level and activity of drug‐metabolizing enzymes and transporters, 2 characteristics associated with low ethnic sensitivity.…”

Section: Discussionsupporting

confidence: 89%

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Surveys/Research Exploring Japanese Phase I Studies in Global Drug Development: Are They Necessary Prior to Joining Global Clinical Trials?

Hirano

Yamada

Tanaka

et al. 2021

Clinical Pharm in Drug Dev

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Section: Discussionsupporting

confidence: 89%

“…However, the general findings and proposals are consistent with those previously published. 2,3,7,9,10 The authors hope that this report will lead to further discussion on this topic with other pharmaceutical companies, academia, and regulatory agencies.…”

Section: Discussionmentioning

confidence: 95%

Surveys/Research Exploring Japanese Phase I Studies in Global Drug Development: Are They Necessary Prior to Joining Global Clinical Trials?

Hirano

Yamada

Tanaka

et al. 2021

Clinical Pharm in Drug Dev

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“…10,11 Of note, 10 mg/kg every 2 weeks was not administered to Chinese patients in this study. However, our previous PPK analyses demonstrated that race (Chinese or Asian versus non-Asian) was not a clinically meaningful covariate for nivolumab exposures, 19 which is consistent with observations of other immuno-oncology drugs, 27 and there were also similar distributions of PK parameters across different races. 28 Even in studies in which flat dosing in an Asian population may be associated with higher exposure, there may not be a significant impact on safety.…”

Section: Discussionsupporting

confidence: 72%

Clinical Benefit‐Risk Assessment of Nivolumab 240 mg Every 2 Weeks in Chinese Patients With Advanced and Metastatic Solid Tumors

Sheng

Zhang

Baudelet

et al. 2021

The Journal of Clinical Pharma

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Nivolumab 240 mg every 2 weeks is approved in China by the National Medical Product Agency for squamous cell carcinoma of the head and neck and gastric cancer, based on population pharmacokinetic (PPK) analyses and benefit-risk assessment of safety/efficacy in solid tumors, including Chinese and global populations. The aim of this assessment was to investigate exposure and risk for adverse events (AEs) with flat dosing compared with weight-based dosing. Nivolumab 240-mg and 3-mg/kg every-2-week exposures in Chinese patients were simulated using PPK modeling, and AEs in Chinese and pooled global populations were compared by dosing regimen, exposure, and weight. The 10-mg/kg every-2-week regimen was included because it is known to be well tolerated. Predicted nivolumab exposure in Chinese patients receiving 240 mg every 2 weeks was ∼25% higher versus 3 mg/kg every 2 weeks, but ∼60% lower versus 10 mg/kg every 2 weeks. Grade 3/4 AE incidence in Chinese patients receiving nivolumab 3 mg/kg every 2 weeks was similar with 240-mg every-2-week dosing and with patients from global populations treated with 3 or 10 mg/kg every 2 weeks. There was no trend toward increased AE incidence with high versus low nivolumab exposure or in global patients of varying body weight receiving 3 or 10 mg/kg every 2 weeks. Objective response rates were similar in Chinese and global patients with squamous and nonsquamous NSCLC. Results showed that benefit-risk profiles with nivolumab 240 mg every 2 weeks were similar to those of the 3-mg/kg every-2-week regimen in Chinese patients and global populations, providing an alternative treatment option to Chinese patients.

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“…Across global regions, bevacizumab dosing is based on body weight, and atezolizumab uses flat dosing that does not require adjustments to account for regional body size differences. The similarity in dosing regimens for Western versus Asian regions is also seen with other mAbs; a survey of 22 biologics (predominantly mAbs) for oncology use approved in Japan, China, and the USA prior to 2018 showed no differences between dosing regimens used in Asian and Western populations [60].…”

Section: Discussionmentioning

confidence: 97%

Atezolizumab and Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma: Pharmacokinetic and Safety Assessments Based on Hepatic Impairment Status and Geographic Region

Shemesh¹,

Chan²,

Shao

et al. 2021

Liver Cancer

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Introduction: Phase 1b GO30140 and phase 3 IMbrave150 studies evaluated first-line atezolizumab + bevacizumab for unresectable hepatocellular carcinoma (HCC). Here, we evaluated pharmacokinetics (PK) and safety by hepatic impairment status and geographic region. Methods: Patients received atezolizumab 1,200 mg + bevacizumab 15 mg/kg IV every 3 weeks. Drug concentrations were evaluated by descriptive statistics and population PK. PK and adverse event frequencies were evaluated by hepatic impairment status and region. Results: 323 IMbrave150 patients and 162 GO30140 patients were PK evaluable. Compared with IMbrave150 patients who had normal hepatic function per the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria (n = 123), patients with mild impairment (n = 171) had a geometric mean ratio (GMR) of 0.92 for cycle 1 atezolizumab area under the concentration-time curve (AUC); patients with moderate impairment (n = 27) had a GMR of 0.88. Patients in Asia ([n = 162] vs. outside [n = 161]) had a GMR of 1.25 for cycle 1 atezolizumab AUC. Compared with GO30140 patients who had normal hepatic function (NCI-ODWG [n = 61]), patients with mild impairment (n = 92) had a GMR of 0.97 for cycle 1 peak bevacizumab concentrations; those with moderate impairment (n = 9) had a GMR of 0.94. Patients in Asia (n = 111) versus outside Asia (n = 51) had a GMR of 0.94 for cycle 1 peak bevacizumab concentration. PK results were generally comparable when evaluated based on additional hepatic functional definitions (Child-Pugh or albumin/bilirubin criteria) or study enrollment in Japan. No associations between atezolizumab PK and HCC etiology were seen. Adverse event frequencies were similar across evaluated groups. Conclusions: IMbrave150 and GO30140 patients with unresectable HCC had varying baseline hepatic impairment and high enrollment from Asia. PK data demonstrated considerable exposure overlap across groups. Treatment was tolerable across groups. No need for dose adjustment based on mild or moderate hepatic impairment or region is recommended based on this analysis.

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Oncology Therapy Drugs in China, Japan, and the United States: Pharmacokinetic Characteristics, Dose Regimens, and Development Strategies

Cited by 9 publications

References 6 publications

Surveys/Research Exploring Japanese Phase I Studies in Global Drug Development: Are They Necessary Prior to Joining Global Clinical Trials?

Surveys/Research Exploring Japanese Phase I Studies in Global Drug Development: Are They Necessary Prior to Joining Global Clinical Trials?

Clinical Benefit‐Risk Assessment of Nivolumab 240 mg Every 2 Weeks in Chinese Patients With Advanced and Metastatic Solid Tumors

Atezolizumab and Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma: Pharmacokinetic and Safety Assessments Based on Hepatic Impairment Status and Geographic Region

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