Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase Ⅰ study.
- Author:
Li ZHANG
1
;
Ji Fang GONG
2
,
3
;
Hong Ming PAN
4
;
Yu Xian BAI
5
;
Tian Shu LIU
6
;
Ying CHENG
7
;
Ya Chi CHEN
8
;
Jia Ying HUANG
9
;
Ting Ting XU
9
;
Fei Jiao GE
9
;
Wan Ling HSU
10
;
Jia SHI
11
;
Xi Chun HU
12
;
Lin SHEN
2
,
3
Author Information
1. Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
2. Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education
3. Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
4. Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China.
5. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China.
6. Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
7. Department of Medical Oncology, Jilin Cancer Hospital, Changchun 130012, China.
8. Clinical Pharmacology, Genentech, Inc., South San Francisco, CA 94080, USA.
9. Oncology, Roche Product Development Shanghai, Shanghai, 201203, China.
10. Department of Statistics, Roche Product Development Shanghai, Shanghai 201203, China.
11. Portfolio Clinical Safety, Roche Product Development Shanghai, Shanghai 201203, China.
12. Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
- Publication Type:Journal Article
- Keywords:
Atezolizumab;
China;
Neoplasms;
Pharmacokinetics
- MeSH:
Adolescent;
Antibodies, Monoclonal, Humanized;
Antineoplastic Agents/therapeutic use*;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*;
Carcinoma, Hepatocellular/drug therapy*;
Cisplatin/therapeutic use*;
Humans;
Liver Neoplasms/drug therapy*;
Lung Neoplasms/pathology*;
Nasopharyngeal Neoplasms/drug therapy*
- From:
Journal of Peking University(Health Sciences)
2022;54(5):971-980
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC).
METHODS:This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC).
RESULTS:This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified.
CONCLUSION:Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
