PMID- 33501654
OWN - NLM
STAT- MEDLINE
DCOM- 20211221
LR  - 20221207
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Print)
IS  - 0091-2700 (Linking)
VI  - 61
IP  - 8
DP  - 2021 Aug
TI  - Clinical Benefit-Risk Assessment of Nivolumab 240 mg Every 2 Weeks in Chinese 
      Patients With Advanced and Metastatic Solid Tumors.
PG  - 1045-1053
LID - 10.1002/jcph.1821 [doi]
AB  - 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  approximately 25% 
      higher versus 3 mg/kg every 2 weeks, but  approximately 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.
CI  - (c) 2021 BMS. The Journal of Clinical Pharmacology published by Wiley Periodicals 
      LLC on behalf of American College of Clinical Pharmacology.
FAU - Sheng, Jennifer
AU  - Sheng J
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Zhang, Jason
AU  - Zhang J
AD  - Bristol Myers Squibb, Lawrenceville, New Jersey, USA.
FAU - Baudelet, Christine
AU  - Baudelet C
AD  - Bristol Myers Squibb, Walloon Brabant, Belgium.
FAU - Roy, Amit
AU  - Roy A
AD  - Bristol Myers Squibb, Lawrenceville, New Jersey, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210214
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - Antineoplastic Agents, Immunological/*administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Asian People
MH  - Bayes Theorem
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy
MH  - China
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Humans
MH  - Lung Neoplasms/drug therapy
MH  - Metabolic Clearance Rate
MH  - Models, Biological
MH  - Nivolumab/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Risk Assessment
PMC - PMC8359491
OTO - NOTNLM
OT  - China
OT  - flat dosing
OT  - nivolumab
OT  - population pharmacokinetics
OT  - solid tumors
COIS- All authors are employees of and hold stock and/or other ownership interests in 
      Bristol Myers Squibb.
EDAT- 2021/01/28 06:00
MHDA- 2021/12/22 06:00
PMCR- 2021/08/12
CRDT- 2021/01/27 05:56
PHST- 2020/10/23 00:00 [received]
PHST- 2021/01/21 00:00 [accepted]
PHST- 2021/01/28 06:00 [pubmed]
PHST- 2021/12/22 06:00 [medline]
PHST- 2021/01/27 05:56 [entrez]
PHST- 2021/08/12 00:00 [pmc-release]
AID - JCPH1821 [pii]
AID - 10.1002/jcph.1821 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2021 Aug;61(8):1045-1053. doi: 10.1002/jcph.1821. Epub 2021 Feb 
      14.