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Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase Ⅰ study
Received date: 2022-07-08
Online published: 2022-10-14
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.
Key words: Atezolizumab; Pharmacokinetics; China; Neoplasms
Li ZHANG , Ji-fang GONG , Hong-ming PAN , Yu-xian BAI , Tian-shu LIU , Ying CHENG , Ya-chi CHEN , Jia-ying HUANG , Ting-ting XU , Fei-jiao GE , Wan-ling HSU , Jane SHI , Xi-chun HU , Lin SHEN . Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase Ⅰ study[J]. Journal of Peking University(Health Sciences), 2022 , 54(5) : 971 -980 . DOI: 10.19723/j.issn.1671-167X.2022.05.026
| 1 | International Agency for Research on Cancer. China (Globocan 2020)[EB/OL]. (2021-03)[2021-05-15] https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf. |
| 2 | Arnold M , Soerjomataram I , Ferlay J , et al. Global incidence of oesophageal cancer by histological subtype in 2012[J]. Gut, 2015, 64 (3): 381- 387. |
| 3 | Salehiniya H , Mohammadian M , Mohammadian-Hafshejani A , et al. Nasopharyngeal cancer in the world: Epidemiology, incidence, mortality and risk factors[J]. World Cancer Res J, 2018, 5 (1): e1046. |
| 4 | Merck. Highlights of prescribing information. Keytruda® (Pembrolizumab)[EB/OL]. (2014)[2022-05-12]. https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf. |
| 5 | Fuchs CS , Doi T , Jang RW , et al. Safety and efficacy of pembro-lizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial[J]. JAMA Oncol, 2018, 4 (5): e180013. |
| 6 | Bristol Myers Squibb Company. Highlights of prescribing information. Opdivo (Nivolumab)[EB/OL]. (2014)[2022-05-03]. https://packageinserts.bms.com/pi/pi_opdivo.pdf. |
| 7 | Ma BBY , Lim WT , Goh BC , et al. Antitumor activity of ni-volumab in recurrent and metastatic nasopharyngeal carcinoma: An international, multicenter study of the Mayo clinic phase 2 consortium (NCI-9742)[J]. J Clin Oncol, 2018, 36 (14): 1412- 1418. |
| 8 | NCCN Clinical Practice Guidelines in Oncology. Non-small cell lung cancer. Version 3.2022[EB/OL]. (2022-03-16)[2022-05]. http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. |
| 9 | Herbst RS , Soria JC , Kowanetz M , et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients[J]. Nature, 2014, 515 (7528): 563- 567. |
| 10 | Weinstock C , Khozin S , Suzman D , et al. U.S. Food and Drug Administration approval summary: Atezolizumab for metastatic non-small cell lung cance[J]. Clin Cancer Res, 2017, 23 (16): 4534- 4539. |
| 11 | Genentech. FDA approves Genentech's Tecentriq plus chemothe-rapy (abraxane and carboplatin) for the initial treatment of metastatic non-squamous non-small cell lung cancer[N/OL]. (2019-12-03)[2021-05-03] https://www.gene.com/media/press-releases/14827/2019-12-03/fda-approves-genentechs-tecentriq-plus-c. |
| 12 | F. Hoffmann-La Roche Ltd. European Commission approves Roche's new Tecentriq-based combination therapy as an initial treatment for most common form of advanced lung cancer[N/OL]. (2019-09-06)[2021-05-11] https://www.roche.com/media/releases/med-cor-2019-09-06.htm. |
| 13 | F. Hoffmann-La Roche Ltd. FDA approves Roche's Tecentriq in combination with Avastin for people with the most common form of liver cancer[N/OL]. (2020-06-02)[2021-05-15] https://www.roche.com/media/releases/med-cor-2020-06-02.htm. |
| 14 | Finn RS , Qin S , Ikeda M , et al. Atezolizumab plus Bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med, 2020, 382 (20): 1894- 1905. |
| 15 | Xu ZY , Brown L , Pan GW , et al. Lifestyle, environmental pollution and lung cancer in cities of Liaoning in northeastern China[J]. Lung Cancer, 1996, 14 (Suppl 1): S149- S160. |
| 16 | Grenade C , Phelps MA , Villalona-Calero MA . Race and ethnicity in cancer therapy: What have we learned?[J]. Clin Pharmacol Ther, 2014, 95 (4): 403- 412. |
| 17 | Genentech. Highlights of prescribing information. Tecentriq®(atezolizumab)[EB/OL]. (2016)[2022-05-15]. https://www.gene.com/download/pdf/tecentriq_prescribing.pdf. |
| 18 | West H , McCleod M , Hussein M , et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): A multicentre, randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2019, 20 (7): 924- 937. |
| 19 | Lee MS , Ryoo BY , Hsu CH , et al. Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): An open-label, multicentre, phase 1b study[J]. Lancet Oncol, 2020, 21 (6): 808- 820. |
| 20 | Zhang T , Xie J , Arai S , et al. The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory can-cers: A meta-analysis[J]. Oncotarget, 2016, 7 (45): 73068- 73079. |
| 21 | Le DT , Kavan P , Kim TW , et al. KEYNOTE-164: Pembrolizu-mab for patients with advanced microsatellite instability high (MSI-H) colorectal cancer[J]. J Clin Oncol, 2018, 36 (Suppl 15): 3514. |
| 22 | Colevas AD , Bahleda R , Braiteh F , et al. Safety and clinical activity of atezolizumab in head and neck cancer: Results from a phase Ⅰ trial[J]. Ann Oncol, 2018, 29 (11): 2247- 2253. |
| 23 | Schiller JH , Harrington D , Belani CP , et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer[J]. N Engl J Med, 2002, 346 (2): 92- 98. |
| 24 | International Agency for Research on Cancer. All cancers (Globocan 2020)[EB/OL]. (2020-12)[2022-05-12] https://gco.iarc.fr/today/data/factsheets/cancers/39-All-cancers-fact-sheet.pdf. |
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