Efficacy, safety and dose selection of AZD3759 in patients with untreated EGFR-mutated non-small-cell lung cancer and central nervous system metastases in China (CTONG1702-Arm 8): a multi-center, single-arm, phase 2 trial
Central nervous system (CNS) metastases is inevitable for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel EGFR-TKI with impressive CNS penetration. We initiated a phase 2, multi-center, umbrella trial (CTONG1702, NCT03574402). The eighth arm asse...
Saved in:
| Published in | EClinicalMedicine Vol. 64; p. 102238 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Elsevier Ltd
01.10.2023
Elsevier |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2589-5370 2589-5370 |
| DOI | 10.1016/j.eclinm.2023.102238 |
Cover
| Abstract | Central nervous system (CNS) metastases is inevitable for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel EGFR-TKI with impressive CNS penetration.
We initiated a phase 2, multi-center, umbrella trial (CTONG1702, NCT03574402). The eighth arm assessed the efficacy and safety of AZD3759 in untreated EGFR-mutated NSCLC with CNS metastases. The primary objective was the objective response rate (ORR). Simon’s minimax two-stage design was used to calculate the sample size. Dose optimal selection was performed using 200- and 300-mg bid cohorts.
Between Oct 18, 2018 and Sep 14, 2020, 30 patients received AZD3759 at 200 mg (n = 15) or 300 mg (n = 15) bid. At data cutoff (Dec 31, 2022), median follow-up was 35.4 months. The primary endpoint was reached, with a confirmed ORR of 70% (21/30) (200 mg, 80%; 300 mg, 60%). The median progression-free survival was 12.9 months (200 mg, 15.8 months; 300 mg, 10.7 months). Grade 3 or 4 treatment-related adverse events occurred in 73% (22/30) of the patients (200 mg: 60%; 300 mg: 87%). 59% (10/17) of the patients developed a T790M mutation at disease progression. The median overall survival was 33.7 months, and 34.1 months and 25.3 months in patient treated with or without osimertinib in a later-line setting, respectively.
AZD3759 showed promising efficacy and tolerable safety as a first-line therapy in EGFR-mutated NSCLC with CNS metastases. The 200-mg bid cohort had better clinical outcomes. Sequential use of AZD3759 and third-generation EGFR-TKIs represents a new option.
Chinese Thoracic Oncology Group (CTONG). |
|---|---|
| AbstractList | Central nervous system (CNS) metastases is inevitable for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel EGFR-TKI with impressive CNS penetration.BackgroundCentral nervous system (CNS) metastases is inevitable for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel EGFR-TKI with impressive CNS penetration.We initiated a phase 2, multi-center, umbrella trial (CTONG1702, NCT03574402). The eighth arm assessed the efficacy and safety of AZD3759 in untreated EGFR-mutated NSCLC with CNS metastases. The primary objective was the objective response rate (ORR). Simon's minimax two-stage design was used to calculate the sample size. Dose optimal selection was performed using 200- and 300-mg bid cohorts.MethodsWe initiated a phase 2, multi-center, umbrella trial (CTONG1702, NCT03574402). The eighth arm assessed the efficacy and safety of AZD3759 in untreated EGFR-mutated NSCLC with CNS metastases. The primary objective was the objective response rate (ORR). Simon's minimax two-stage design was used to calculate the sample size. Dose optimal selection was performed using 200- and 300-mg bid cohorts.Between Oct 18, 2018 and Sep 14, 2020, 30 patients received AZD3759 at 200 mg (n = 15) or 300 mg (n = 15) bid. At data cutoff (Dec 31, 2022), median follow-up was 35.4 months. The primary endpoint was reached, with a confirmed ORR of 70% (21/30) (200 mg, 80%; 300 mg, 60%). The median progression-free survival was 12.9 months (200 mg, 15.8 months; 300 mg, 10.7 months). Grade 3 or 4 treatment-related adverse events occurred in 73% (22/30) of the patients (200 mg: 60%; 300 mg: 87%). 59% (10/17) of the patients developed a T790M mutation at disease progression. The median overall survival was 33.7 months, and 34.1 months and 25.3 months in patient treated with or without osimertinib in a later-line setting, respectively.FindingsBetween Oct 18, 2018 and Sep 14, 2020, 30 patients received AZD3759 at 200 mg (n = 15) or 300 mg (n = 15) bid. At data cutoff (Dec 31, 2022), median follow-up was 35.4 months. The primary endpoint was reached, with a confirmed ORR of 70% (21/30) (200 mg, 80%; 300 mg, 60%). The median progression-free survival was 12.9 months (200 mg, 15.8 months; 300 mg, 10.7 months). Grade 3 or 4 treatment-related adverse events occurred in 73% (22/30) of the patients (200 mg: 60%; 300 mg: 87%). 59% (10/17) of the patients developed a T790M mutation at disease progression. The median overall survival was 33.7 months, and 34.1 months and 25.3 months in patient treated with or without osimertinib in a later-line setting, respectively.AZD3759 showed promising efficacy and tolerable safety as a first-line therapy in EGFR-mutated NSCLC with CNS metastases. The 200-mg bid cohort had better clinical outcomes. Sequential use of AZD3759 and third-generation EGFR-TKIs represents a new option.InterpretationAZD3759 showed promising efficacy and tolerable safety as a first-line therapy in EGFR-mutated NSCLC with CNS metastases. The 200-mg bid cohort had better clinical outcomes. Sequential use of AZD3759 and third-generation EGFR-TKIs represents a new option.Chinese Thoracic Oncology Group (CTONG).FundingChinese Thoracic Oncology Group (CTONG). SummaryBackgroundCentral nervous system (CNS) metastases is inevitable for epidermal growth factor receptor ( EGFR)-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel EGFR-TKI with impressive CNS penetration. MethodsWe initiated a phase 2, multi-center, umbrella trial (CTONG1702, NCT03574402). The eighth arm assessed the efficacy and safety of AZD3759 in untreated EGFR-mutated NSCLC with CNS metastases. The primary objective was the objective response rate (ORR). Simon’s minimax two-stage design was used to calculate the sample size. Dose optimal selection was performed using 200- and 300-mg bid cohorts. FindingsBetween Oct 18, 2018 and Sep 14, 2020, 30 patients received AZD3759 at 200 mg (n = 15) or 300 mg (n = 15) bid. At data cutoff (Dec 31, 2022), median follow-up was 35.4 months. The primary endpoint was reached, with a confirmed ORR of 70% (21/30) (200 mg, 80%; 300 mg, 60%). The median progression-free survival was 12.9 months (200 mg, 15.8 months; 300 mg, 10.7 months). Grade 3 or 4 treatment-related adverse events occurred in 73% (22/30) of the patients (200 mg: 60%; 300 mg: 87%). 59% (10/17) of the patients developed a T790M mutation at disease progression. The median overall survival was 33.7 months, and 34.1 months and 25.3 months in patient treated with or without osimertinib in a later-line setting, respectively. InterpretationAZD3759 showed promising efficacy and tolerable safety as a first-line therapy in EGFR-mutated NSCLC with CNS metastases. The 200-mg bid cohort had better clinical outcomes. Sequential use of AZD3759 and third-generation EGFR-TKIs represents a new option. FundingChinese Thoracic Oncology Group (CTONG). Central nervous system (CNS) metastases is inevitable for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel EGFR-TKI with impressive CNS penetration. We initiated a phase 2, multi-center, umbrella trial (CTONG1702, NCT03574402). The eighth arm assessed the efficacy and safety of AZD3759 in untreated EGFR-mutated NSCLC with CNS metastases. The primary objective was the objective response rate (ORR). Simon’s minimax two-stage design was used to calculate the sample size. Dose optimal selection was performed using 200- and 300-mg bid cohorts. Between Oct 18, 2018 and Sep 14, 2020, 30 patients received AZD3759 at 200 mg (n = 15) or 300 mg (n = 15) bid. At data cutoff (Dec 31, 2022), median follow-up was 35.4 months. The primary endpoint was reached, with a confirmed ORR of 70% (21/30) (200 mg, 80%; 300 mg, 60%). The median progression-free survival was 12.9 months (200 mg, 15.8 months; 300 mg, 10.7 months). Grade 3 or 4 treatment-related adverse events occurred in 73% (22/30) of the patients (200 mg: 60%; 300 mg: 87%). 59% (10/17) of the patients developed a T790M mutation at disease progression. The median overall survival was 33.7 months, and 34.1 months and 25.3 months in patient treated with or without osimertinib in a later-line setting, respectively. AZD3759 showed promising efficacy and tolerable safety as a first-line therapy in EGFR-mutated NSCLC with CNS metastases. The 200-mg bid cohort had better clinical outcomes. Sequential use of AZD3759 and third-generation EGFR-TKIs represents a new option. Chinese Thoracic Oncology Group (CTONG). |
| ArticleNumber | 102238 |
| Author | Wang, Zhen Zheng, Ming-Ying Bai, Xiao-Yan Li, Yang-Si Xu, Chong-Rui Dong, Xiao-Rong Yang, Ming-Yi Wu, Yi-Long Zhou, Qing Du, Yingying Wang, Bin-Chao Huang, Jie Zheng, Mei-Mei Li, Anna Yang, Jin-Ji Lu, Chang Yan, Hong-Hong Chu, Qian Chen, Hua-Jun Maggie Liu, Si-Yang Cui, Jiu-Wei Sun, Yue-Li Wei, Xue-Wu Xu, Bing-Fei Deng, Jia-Yi Zhong, Wen-Zhao |
| Author_xml | – sequence: 1 givenname: Si-Yang orcidid: 0000-0002-3837-0758 surname: Maggie Liu fullname: Maggie Liu, Si-Yang organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 2 givenname: Xiao-Rong surname: Dong fullname: Dong, Xiao-Rong organization: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China – sequence: 3 givenname: Zhen surname: Wang fullname: Wang, Zhen organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 4 givenname: Yingying surname: Du fullname: Du, Yingying organization: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China – sequence: 5 givenname: Jiu-Wei surname: Cui fullname: Cui, Jiu-Wei organization: Cancer Center, The First Hospital of Jilin University, Jilin University, Changchun 130021, China – sequence: 6 givenname: Qian surname: Chu fullname: Chu, Qian organization: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China – sequence: 7 givenname: Bing-Fei surname: Xu fullname: Xu, Bing-Fei organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 8 givenname: Ming-Ying surname: Zheng fullname: Zheng, Ming-Ying organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 9 givenname: Jia-Yi surname: Deng fullname: Deng, Jia-Yi organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 10 givenname: Chang orcidid: 0000-0001-6504-6083 surname: Lu fullname: Lu, Chang organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 11 givenname: Xue-Wu surname: Wei fullname: Wei, Xue-Wu organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 12 givenname: Yang-Si surname: Li fullname: Li, Yang-Si organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 13 givenname: Mei-Mei surname: Zheng fullname: Zheng, Mei-Mei organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 14 givenname: Ming-Yi surname: Yang fullname: Yang, Ming-Yi organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 15 givenname: Jie surname: Huang fullname: Huang, Jie organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 16 givenname: Anna surname: Li fullname: Li, Anna organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 17 givenname: Xiao-Yan surname: Bai fullname: Bai, Xiao-Yan organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 18 givenname: Yue-Li surname: Sun fullname: Sun, Yue-Li organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 19 givenname: Chong-Rui orcidid: 0000-0002-3474-2809 surname: Xu fullname: Xu, Chong-Rui organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 20 givenname: Bin-Chao surname: Wang fullname: Wang, Bin-Chao organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 21 givenname: Hua-Jun surname: Chen fullname: Chen, Hua-Jun organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 22 givenname: Jin-Ji surname: Yang fullname: Yang, Jin-Ji organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 23 givenname: Hong-Hong surname: Yan fullname: Yan, Hong-Hong organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 24 givenname: Wen-Zhao surname: Zhong fullname: Zhong, Wen-Zhao organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 25 givenname: Qing surname: Zhou fullname: Zhou, Qing email: gzzhouqing@126.com organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China – sequence: 26 givenname: Yi-Long orcidid: 0000-0002-3611-0258 surname: Wu fullname: Wu, Yi-Long email: syylwu@live.cn organization: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China |
| BookMark | eNqVkt9qFDEUxgepYK19Ay9yWaGzJpn_RSzLul2FYkHrjTchm5zZzZpk1iSzsm_TZ-mL-CpmnBVUkCIMJDNzvt85-fI9TY5sZyFJnhM8IZiULzcTEFpZM6GYZvETpVn9KDmmRd2kRVbho9_2T5JT7zcYY4rzuinxcfJ93rZKcLE_R563EPaIW4lk5wF50CCC6izqWjT9_CarigYpi7Y8KLDBo28qrO_vehsc8AASzRdXH1LTh58vccrUG651KkBrpHu7QoJbAW7ocH8nIsJxjSy4Xdd75Pc-gEEGAvfxAT-0mq2V5ehsdnvzfkEqTNOpM6h-cYE4Mr0OKh0o4OLsyq40pNyZc7RdRzmiKDjF9bPkccu1h9PDepJ8uprfzt6m1zeLd7PpdSqKvAmppDSvSkrKZckrzDmJ7nBeNFLgJRSkWgpcQ1tjKght5BI3BS5lW0INMm5lnp0klyN32y8NyMPp2NYpw92edVyxP_9YtWarbscILnKSV0UknB0Irvvagw_MKD94xy1EgxitK1IWZVPVsfRiLBWu895By4SKrserimilI5MN0WAbNkaDDdFgYzSiOP9L_GvIB2SvRxlEF3cKHPMixkCAVC7GhMlO_S9gqInZ019gD37T9c7GG2KEecow-ziEdsgszTDOSVFFwKt_Ax7u_wOMgAP3 |
| CitedBy_id | crossref_primary_10_1016_j_medj_2024_09_002 crossref_primary_10_3390_cancers16122180 crossref_primary_10_2174_0115680096276133231201061114 crossref_primary_10_1038_s41591_025_03538_5 crossref_primary_10_1111_1759_7714_15317 |
| Cites_doi | 10.1158/1078-0432.CCR-19-1871 10.1016/j.lungcan.2015.01.020 10.1016/j.jtho.2021.07.026 10.1016/j.jtho.2022.07.1143 10.1158/1078-0432.CCR-22-1585 10.1200/JCO.22.00371 10.1016/S2213-2600(17)30385-5 10.1016/j.lungcan.2021.09.009 10.1200/JCO.2018.78.3118 10.1200/JCO.2023.41.16_suppl.9001 10.1056/NEJMoa1612674 10.1200/JCO.21.02641 10.1200/JCO.19.00457 10.1021/acs.jmedchem.5b01073 10.1186/s13045-023-01436-2 10.2217/fon-2020-0740 10.1126/scitranslmed.aag0976 10.1016/j.jocn.2015.11.012 10.1016/S2213-2600(22)00168-0 10.1056/NEJMoa1713137 10.1056/NEJMp2109826 10.3389/fonc.2023.1144056 10.1200/JCO.2022.40.16_suppl.9096 10.1016/S2213-2600(17)30378-8 10.1016/j.cllc.2022.05.009 |
| ContentType | Journal Article |
| Copyright | 2023 The Author(s) The Author(s) 2023 The Author(s). 2023 The Author(s) 2023 |
| Copyright_xml | – notice: 2023 The Author(s) – notice: The Author(s) – notice: 2023 The Author(s). – notice: 2023 The Author(s) 2023 |
| DBID | 6I. AAFTH AAYXX CITATION 7X8 5PM |
| DOI | 10.1016/j.eclinm.2023.102238 |
| DatabaseName | ScienceDirect Open Access Titles Elsevier:ScienceDirect:Open Access CrossRef MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 2589-5370 |
| EndPage | 102238 |
| ExternalDocumentID | PMC10541475 10_1016_j_eclinm_2023_102238 S2589537023004157 1_s2_0_S2589537023004157 |
| GrantInformation_xml | – fundername: Chinese Thoracic Oncology Group |
| GroupedDBID | .1- .FO 0R~ 53G AAEDW AALRI AAMRU AAXUO AAYWO ABMAC ACLIJ ACVFH ADBBV ADCNI ADVLN AEUPX AEXQZ AFPUW AFRHN AFTJW AIGII AITUG AJUYK AKBMS AKYEP ALMA_UNASSIGNED_HOLDINGS AMRAJ AOIJS APXCP BCNDV EBS EJD FDB GROUPED_DOAJ HYE M41 OK1 ROL RPM SSZ Z5R 0SF 6I. AACTN NCXOZ AAFTH AAYXX CITATION 7X8 5PM |
| ID | FETCH-LOGICAL-c549t-d22476216b6a70aa1896aa59dc0be517bc08ef802c129db09506df6e8ed950d43 |
| ISSN | 2589-5370 |
| IngestDate | Thu Aug 21 18:36:15 EDT 2025 Thu Jul 10 21:20:21 EDT 2025 Thu Apr 24 22:56:25 EDT 2025 Tue Jul 01 01:50:31 EDT 2025 Sun Apr 06 06:53:01 EDT 2025 Tue Feb 25 20:06:20 EST 2025 Tue Aug 26 20:24:24 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Keywords | EGFR mutation CNS metastasis AZD3759 Lung cancer First-line setting |
| Language | English |
| License | This is an open access article under the CC BY-NC-ND license. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c549t-d22476216b6a70aa1896aa59dc0be517bc08ef802c129db09506df6e8ed950d43 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. |
| ORCID | 0000-0001-6504-6083 0000-0002-3474-2809 0000-0002-3837-0758 0000-0002-3611-0258 |
| OpenAccessLink | http://dx.doi.org/10.1016/j.eclinm.2023.102238 |
| PQID | 2871656978 |
| PQPubID | 23479 |
| PageCount | 1 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_10541475 proquest_miscellaneous_2871656978 crossref_citationtrail_10_1016_j_eclinm_2023_102238 crossref_primary_10_1016_j_eclinm_2023_102238 elsevier_sciencedirect_doi_10_1016_j_eclinm_2023_102238 elsevier_clinicalkeyesjournals_1_s2_0_S2589537023004157 elsevier_clinicalkey_doi_10_1016_j_eclinm_2023_102238 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2023-10-01 |
| PublicationDateYYYYMMDD | 2023-10-01 |
| PublicationDate_xml | – month: 10 year: 2023 text: 2023-10-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationTitle | EClinicalMedicine |
| PublicationYear | 2023 |
| Publisher | Elsevier Ltd Elsevier |
| Publisher_xml | – name: Elsevier Ltd – name: Elsevier |
| References | Reungwetwattana, Nakagawa, Cho (bib8) 2018 Lu, Dong, Jian (bib10) 2022; 40 Liu, Zheng, Pan, Liu, Li, Wu (bib22) 2023; 16 Zhou, Wang, Yu (bib25) 2023; 41 Zeng, Wang, Cheng (bib12) 2015; 58 Yang, Kim, Kim (bib27) 2020; 38 Shah, Rahman, Theoret, Pazdur (bib16) 2021; 385 Mok, Wu, Ahn (bib2) 2017; 376 Brower, Saha, Rosenberg, Hullett, Ian Robins (bib1) 2016; 27 Yang, Yan, Wu (bib3) 2017; 5 Popat, Jung, Lee (bib30) 2021; 162 Soria, Ohe, Vansteenkiste (bib5) 2018; 378 Liu, Yan, Wei (bib20) 2022; 23 Fourie Zirkelbach, Shah, Vallejo (bib15) 2022; 40 Murphy, Halford, Symeonides (bib18) 2023; 13 Ozcan, Singh, Vredenburgh (bib21) 2023; 29 Colclough, Chen, Johnström (bib11) 2021; 27 Yamaguchi, Wakuda, Fukuda (bib28) 2021; 16 Lu, Dong, Jian (bib7) 2022; 40 bib26 Yang, Guo, Wang (bib13) 2016; 8 Ahn, Kim, Cho (bib14) 2017; 5 bib19 Rangachari, Yamaguchi, VanderLaan (bib4) 2015; 88 Hochmair, Morabito, Hao (bib29) 2020; 16 Shi, Chen, Wang (bib6) 2022; 10 bib17 Peled, Kian, Inbar (bib23) 2022; 4 (bib24) 2022; 33 Shi, Chen, Wang (bib9) 2022; 17 Colclough (10.1016/j.eclinm.2023.102238_bib11) 2021; 27 Ahn (10.1016/j.eclinm.2023.102238_bib14) 2017; 5 Liu (10.1016/j.eclinm.2023.102238_bib22) 2023; 16 Shi (10.1016/j.eclinm.2023.102238_bib6) 2022; 10 Popat (10.1016/j.eclinm.2023.102238_bib30) 2021; 162 Mok (10.1016/j.eclinm.2023.102238_bib2) 2017; 376 Lu (10.1016/j.eclinm.2023.102238_bib10) 2022; 40 Zhou (10.1016/j.eclinm.2023.102238_bib25) 2023; 41 Lu (10.1016/j.eclinm.2023.102238_bib7) 2022; 40 Reungwetwattana (10.1016/j.eclinm.2023.102238_bib8) 2018 Brower (10.1016/j.eclinm.2023.102238_bib1) 2016; 27 Peled (10.1016/j.eclinm.2023.102238_bib23) 2022; 4 Yang (10.1016/j.eclinm.2023.102238_bib3) 2017; 5 Shah (10.1016/j.eclinm.2023.102238_bib16) 2021; 385 Murphy (10.1016/j.eclinm.2023.102238_bib18) 2023; 13 Zeng (10.1016/j.eclinm.2023.102238_bib12) 2015; 58 Ozcan (10.1016/j.eclinm.2023.102238_bib21) 2023; 29 (10.1016/j.eclinm.2023.102238_bib24) 2022; 33 Yamaguchi (10.1016/j.eclinm.2023.102238_bib28) 2021; 16 Shi (10.1016/j.eclinm.2023.102238_bib9) 2022; 17 Hochmair (10.1016/j.eclinm.2023.102238_bib29) 2020; 16 Yang (10.1016/j.eclinm.2023.102238_bib13) 2016; 8 Soria (10.1016/j.eclinm.2023.102238_bib5) 2018; 378 Liu (10.1016/j.eclinm.2023.102238_bib20) 2022; 23 Yang (10.1016/j.eclinm.2023.102238_bib27) 2020; 38 Rangachari (10.1016/j.eclinm.2023.102238_bib4) 2015; 88 Fourie Zirkelbach (10.1016/j.eclinm.2023.102238_bib15) 2022; 40 |
| References_xml | – volume: 27 start-page: 130 year: 2016 end-page: 137 ident: bib1 article-title: Management of leptomeningeal metastases: prognostic factors and associated outcomes publication-title: J Clin Neurosci – ident: bib17 article-title: Project Optimus | FDA – volume: 88 start-page: 108 year: 2015 end-page: 111 ident: bib4 article-title: Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers publication-title: Lung Cancer – volume: 40 start-page: 3489 year: 2022 end-page: 3500 ident: bib15 article-title: Improving dose-optimization processes used in oncology drug development to minimize toxicity and maximize benefit to patients publication-title: J Clin Oncol – volume: 13 year: 2023 ident: bib18 article-title: Project Optimus, an FDA initiative: considerations for cancer drug development internationally, from an academic perspective publication-title: Front Oncol – volume: 16 start-page: 2799 year: 2020 end-page: 2808 ident: bib29 article-title: Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: final analysis of the GioTag study publication-title: Future Oncol – volume: 17 start-page: 1297 year: 2022 end-page: 1305 ident: bib9 article-title: Central nervous system efficacy of furmonertinib (AST2818) versus gefitinib as first-line treatment for EGFR-mutated NSCLC: results from the FURLONG study publication-title: J Thorac Oncol – volume: 16 start-page: 2121 year: 2021 end-page: 2132 ident: bib28 article-title: A phase II study of osimertinib for radiotherapy-naive central nervous system metastasis from NSCLC: results for the T790M cohort of the OCEAN study (LOGIK1603/WJOG9116L) publication-title: J Thorac Oncol – volume: 5 start-page: e34 year: 2017 ident: bib3 article-title: BRAIN study: it is hard to draw a conclusion - authors' reply publication-title: Lancet Respir Med – volume: 8 year: 2016 ident: bib13 article-title: AZD3759, a BBB-penetrating EGFR inhibitor for the treatment of EGFR mutant NSCLC with CNS metastases publication-title: Sci Transl Med – year: 2018 ident: bib8 article-title: CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer publication-title: J Clin Oncol – volume: 27 start-page: 189 year: 2021 end-page: 201 ident: bib11 article-title: Preclinical comparison of the blood-brain barrier permeability of osimertinib with other EGFR TKIs publication-title: Clin Cancer Res – volume: 10 start-page: 1019 year: 2022 end-page: 1028 ident: bib6 article-title: Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study publication-title: Lancet Respir Med – volume: 16 start-page: 40 year: 2023 ident: bib22 article-title: Emerging evidence and treatment paradigm of non-small cell lung cancer publication-title: J Hematol Oncol – volume: 385 start-page: 1445 year: 2021 end-page: 1447 ident: bib16 article-title: The drug-dosing conundrum in oncology - when less is more publication-title: N Engl J Med – volume: 162 start-page: 9 year: 2021 end-page: 15 ident: bib30 article-title: Sequential afatinib and osimertinib in patients with EGFR mutation-positive NSCLC and acquired T790M: a global non-interventional study (UpSwinG) publication-title: Lung Cancer – volume: 5 start-page: 891 year: 2017 end-page: 902 ident: bib14 article-title: Activity and safety of AZD3759 in EGFR-mutant non-small-cell lung cancer with CNS metastases (BLOOM): a phase 1, open-label, dose-escalation and dose-expansion study publication-title: Lancet Respir Med – ident: bib26 article-title: Tagrisso plus chemotherapy demonstrated strong improvement in progression-free survival for patients with EGFR-mutated advanced lung cancer in FLAURA2 Phase III trial – volume: 33 year: 2022 ident: bib24 article-title: 367P High-dose aumolertinib in EGFR-mutant NSCLC patients with brain metastases: primary data from ACHIEVE publication-title: Ann Oncol – volume: 40 start-page: 9096 year: 2022 ident: bib10 article-title: Aumolertinib activity in patients with CNS metastases and EGFR-mutated NSCLC treated in the randomized double-blind phase III trial (AENEAS) publication-title: J Clin Oncol – volume: 38 start-page: 538 year: 2020 end-page: 547 ident: bib27 article-title: Osimertinib in patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer and leptomeningeal metastases: the BLOOM study publication-title: J Clin Oncol – volume: 40 start-page: 3162 year: 2022 end-page: 3171 ident: bib7 article-title: AENEAS: a randomized phase III trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or MetastaticNon-small-cell lung cancer with EGFR exon 19 deletion or L858R mutations publication-title: J Clin Oncol – volume: 378 start-page: 113 year: 2018 end-page: 125 ident: bib5 article-title: Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer publication-title: N Engl J Med – volume: 58 start-page: 8200 year: 2015 end-page: 8215 ident: bib12 article-title: Discovery and evaluation of clinical candidate AZD3759, a potent, oral active, central nervous system-penetrant, epidermal growth factor receptor tyrosine kinase inhibitor publication-title: J Med Chem – volume: 23 start-page: e395 year: 2022 end-page: e399 ident: bib20 article-title: Biomarker-driven studies with multi-targets and multi-drugs by next-generation sequencing for patients with non-small-cell lung cancer: an open-label, multi-center, phase II adaptive umbrella trial and a real-world observational study (CTONG1702&CTONG1705) publication-title: Clin Lung Cancer – volume: 41 start-page: 9001 year: 2023 ident: bib25 article-title: Randomized phase 3 study of first-line AZD3759 (zorifertinib) versus gefitinib or erlotinib in EGFR-mutant (EGFRm+) non–small-cell lung cancer (NSCLC) with central nervous system (CNS) metastasis publication-title: J Clin Oncol – volume: 376 start-page: 629 year: 2017 end-page: 640 ident: bib2 article-title: Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer publication-title: N Engl J Med – ident: bib19 article-title: Optimizing the dosage of human prescription drugs and biological products for the treatment of oncologic diseases – volume: 4 year: 2022 ident: bib23 article-title: Osimertinib in advanced EGFR-mutant lung adenocarcinoma with asymptomatic brain metastases: an open-label, 3-arm, phase II pilot study publication-title: Neurooncol Adv – volume: 29 start-page: 11 year: 2023 end-page: 29 ident: bib21 article-title: Leptomeningeal metastasis from non-small cell lung cancer and current landscape of treatments publication-title: Clin Cancer Res – volume: 27 start-page: 189 issue: 1 year: 2021 ident: 10.1016/j.eclinm.2023.102238_bib11 article-title: Preclinical comparison of the blood-brain barrier permeability of osimertinib with other EGFR TKIs publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-19-1871 – volume: 88 start-page: 108 issue: 1 year: 2015 ident: 10.1016/j.eclinm.2023.102238_bib4 article-title: Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers publication-title: Lung Cancer doi: 10.1016/j.lungcan.2015.01.020 – volume: 16 start-page: 2121 issue: 12 year: 2021 ident: 10.1016/j.eclinm.2023.102238_bib28 article-title: A phase II study of osimertinib for radiotherapy-naive central nervous system metastasis from NSCLC: results for the T790M cohort of the OCEAN study (LOGIK1603/WJOG9116L) publication-title: J Thorac Oncol doi: 10.1016/j.jtho.2021.07.026 – volume: 17 start-page: 1297 issue: 11 year: 2022 ident: 10.1016/j.eclinm.2023.102238_bib9 article-title: Central nervous system efficacy of furmonertinib (AST2818) versus gefitinib as first-line treatment for EGFR-mutated NSCLC: results from the FURLONG study publication-title: J Thorac Oncol doi: 10.1016/j.jtho.2022.07.1143 – volume: 4 issue: 1 year: 2022 ident: 10.1016/j.eclinm.2023.102238_bib23 article-title: Osimertinib in advanced EGFR-mutant lung adenocarcinoma with asymptomatic brain metastases: an open-label, 3-arm, phase II pilot study publication-title: Neurooncol Adv – volume: 29 start-page: 11 issue: 1 year: 2023 ident: 10.1016/j.eclinm.2023.102238_bib21 article-title: Leptomeningeal metastasis from non-small cell lung cancer and current landscape of treatments publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-22-1585 – volume: 40 start-page: 3489 issue: 30 year: 2022 ident: 10.1016/j.eclinm.2023.102238_bib15 article-title: Improving dose-optimization processes used in oncology drug development to minimize toxicity and maximize benefit to patients publication-title: J Clin Oncol doi: 10.1200/JCO.22.00371 – volume: 5 start-page: e34 issue: 11 year: 2017 ident: 10.1016/j.eclinm.2023.102238_bib3 article-title: BRAIN study: it is hard to draw a conclusion - authors' reply publication-title: Lancet Respir Med doi: 10.1016/S2213-2600(17)30385-5 – volume: 162 start-page: 9 year: 2021 ident: 10.1016/j.eclinm.2023.102238_bib30 article-title: Sequential afatinib and osimertinib in patients with EGFR mutation-positive NSCLC and acquired T790M: a global non-interventional study (UpSwinG) publication-title: Lung Cancer doi: 10.1016/j.lungcan.2021.09.009 – year: 2018 ident: 10.1016/j.eclinm.2023.102238_bib8 article-title: CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer publication-title: J Clin Oncol doi: 10.1200/JCO.2018.78.3118 – volume: 41 start-page: 9001 issue: 16_suppl year: 2023 ident: 10.1016/j.eclinm.2023.102238_bib25 article-title: Randomized phase 3 study of first-line AZD3759 (zorifertinib) versus gefitinib or erlotinib in EGFR-mutant (EGFRm+) non–small-cell lung cancer (NSCLC) with central nervous system (CNS) metastasis publication-title: J Clin Oncol doi: 10.1200/JCO.2023.41.16_suppl.9001 – volume: 376 start-page: 629 issue: 7 year: 2017 ident: 10.1016/j.eclinm.2023.102238_bib2 article-title: Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer publication-title: N Engl J Med doi: 10.1056/NEJMoa1612674 – volume: 40 start-page: 3162 issue: 27 year: 2022 ident: 10.1016/j.eclinm.2023.102238_bib7 article-title: AENEAS: a randomized phase III trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or MetastaticNon-small-cell lung cancer with EGFR exon 19 deletion or L858R mutations publication-title: J Clin Oncol doi: 10.1200/JCO.21.02641 – volume: 38 start-page: 538 issue: 6 year: 2020 ident: 10.1016/j.eclinm.2023.102238_bib27 article-title: Osimertinib in patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer and leptomeningeal metastases: the BLOOM study publication-title: J Clin Oncol doi: 10.1200/JCO.19.00457 – volume: 58 start-page: 8200 issue: 20 year: 2015 ident: 10.1016/j.eclinm.2023.102238_bib12 article-title: Discovery and evaluation of clinical candidate AZD3759, a potent, oral active, central nervous system-penetrant, epidermal growth factor receptor tyrosine kinase inhibitor publication-title: J Med Chem doi: 10.1021/acs.jmedchem.5b01073 – volume: 16 start-page: 40 issue: 1 year: 2023 ident: 10.1016/j.eclinm.2023.102238_bib22 article-title: Emerging evidence and treatment paradigm of non-small cell lung cancer publication-title: J Hematol Oncol doi: 10.1186/s13045-023-01436-2 – volume: 16 start-page: 2799 issue: 34 year: 2020 ident: 10.1016/j.eclinm.2023.102238_bib29 article-title: Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: final analysis of the GioTag study publication-title: Future Oncol doi: 10.2217/fon-2020-0740 – volume: 8 issue: 368 year: 2016 ident: 10.1016/j.eclinm.2023.102238_bib13 article-title: AZD3759, a BBB-penetrating EGFR inhibitor for the treatment of EGFR mutant NSCLC with CNS metastases publication-title: Sci Transl Med doi: 10.1126/scitranslmed.aag0976 – volume: 27 start-page: 130 year: 2016 ident: 10.1016/j.eclinm.2023.102238_bib1 article-title: Management of leptomeningeal metastases: prognostic factors and associated outcomes publication-title: J Clin Neurosci doi: 10.1016/j.jocn.2015.11.012 – volume: 10 start-page: 1019 issue: 11 year: 2022 ident: 10.1016/j.eclinm.2023.102238_bib6 article-title: Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study publication-title: Lancet Respir Med doi: 10.1016/S2213-2600(22)00168-0 – volume: 33 year: 2022 ident: 10.1016/j.eclinm.2023.102238_bib24 article-title: 367P High-dose aumolertinib in EGFR-mutant NSCLC patients with brain metastases: primary data from ACHIEVE publication-title: Ann Oncol – volume: 378 start-page: 113 issue: 2 year: 2018 ident: 10.1016/j.eclinm.2023.102238_bib5 article-title: Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer publication-title: N Engl J Med doi: 10.1056/NEJMoa1713137 – volume: 385 start-page: 1445 issue: 16 year: 2021 ident: 10.1016/j.eclinm.2023.102238_bib16 article-title: The drug-dosing conundrum in oncology - when less is more publication-title: N Engl J Med doi: 10.1056/NEJMp2109826 – volume: 13 year: 2023 ident: 10.1016/j.eclinm.2023.102238_bib18 article-title: Project Optimus, an FDA initiative: considerations for cancer drug development internationally, from an academic perspective publication-title: Front Oncol doi: 10.3389/fonc.2023.1144056 – volume: 40 start-page: 9096 issue: 16_suppl year: 2022 ident: 10.1016/j.eclinm.2023.102238_bib10 article-title: Aumolertinib activity in patients with CNS metastases and EGFR-mutated NSCLC treated in the randomized double-blind phase III trial (AENEAS) publication-title: J Clin Oncol doi: 10.1200/JCO.2022.40.16_suppl.9096 – volume: 5 start-page: 891 issue: 11 year: 2017 ident: 10.1016/j.eclinm.2023.102238_bib14 article-title: Activity and safety of AZD3759 in EGFR-mutant non-small-cell lung cancer with CNS metastases (BLOOM): a phase 1, open-label, dose-escalation and dose-expansion study publication-title: Lancet Respir Med doi: 10.1016/S2213-2600(17)30378-8 – volume: 23 start-page: e395 issue: 7 year: 2022 ident: 10.1016/j.eclinm.2023.102238_bib20 article-title: Biomarker-driven studies with multi-targets and multi-drugs by next-generation sequencing for patients with non-small-cell lung cancer: an open-label, multi-center, phase II adaptive umbrella trial and a real-world observational study (CTONG1702&CTONG1705) publication-title: Clin Lung Cancer doi: 10.1016/j.cllc.2022.05.009 |
| SSID | ssj0002048960 |
| Score | 2.2963636 |
| Snippet | Central nervous system (CNS) metastases is inevitable for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). AZD3759 is a novel... SummaryBackgroundCentral nervous system (CNS) metastases is inevitable for epidermal growth factor receptor ( EGFR)-mutant non-small cell lung cancer (NSCLC).... |
| SourceID | pubmedcentral proquest crossref elsevier |
| SourceType | Open Access Repository Aggregation Database Enrichment Source Index Database Publisher |
| StartPage | 102238 |
| SubjectTerms | AZD3759 CNS metastasis EGFR mutation First-line setting Internal Medicine Lung cancer |
| Title | Efficacy, safety and dose selection of AZD3759 in patients with untreated EGFR-mutated non-small-cell lung cancer and central nervous system metastases in China (CTONG1702-Arm 8): a multi-center, single-arm, phase 2 trial |
| URI | https://www.clinicalkey.com/#!/content/1-s2.0-S2589537023004157 https://www.clinicalkey.es/playcontent/1-s2.0-S2589537023004157 https://dx.doi.org/10.1016/j.eclinm.2023.102238 https://www.proquest.com/docview/2871656978 https://pubmed.ncbi.nlm.nih.gov/PMC10541475 |
| Volume | 64 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnZ3bTtwwEIYtSqWqN1WPKj3JlYrUKhjl5Bx6hziqKrSioAI3lhM7sGjJIrJ70T4Nz8Ir9AH6Kp2xnd0sUEF7s1p2sZPNfI7Hk3_GhLyLeRFUHEZamXDN4kJrJlUELOtQpTLSSiqj8t1KNnbjT3t8b2bmV0e1NBoWi-XPa_NK_seq8BnYFbNk_8Gy407hA3gP9oVXsDC83srGq1j_QZbmOjWyQvUlxsEVatAbs8GNcweXDlailOfepJCqzWqbXw7nl_xRbeTm4Hqurq9ts5PR0PxRD2rWnMh-n2F03-uPMD0XITGyS9vUaTu9Gm45KKa1haFxX2oJbmdj1F52j27zuHjny9Z6kILNgC8vmw9zm2ttVI0M-7IAYfyiD-Y8M7CeHkFHXuiZDUamniS4oqb9zUsCgU15eNjT3ufeyAR3e2xfugkaXXYnQt7ryQHbHky--O5C5wdHk_S4FdPDPpzPj3aOdyGScCK2c3E752TYKc_cW0Oe5YxHds-SdiKw5dSvzCk2vHG8qDFXFYsXhBEWvAhtVZpL1bq_bi6DxxoHccrvkLthCg5dZ51_bJ78xhksG9s0TqM1vNr139ykzjJoWsTb8Yp2HpIHbjlDlyybj8iMrh-Te609npDfLaIL1AJKAR2KgNIxoHRQUQco7dW0BZQioBfnYzhpF046DSdFOKmFE49wce7OlzowqQWTTsDEQxkw6fspLGn24SOVtIsknPsYyAVqcKQhNTg-JbtrqzvLG8ztKcJKHudDpsBlhfk_SIpEpr6UAdhCSp6r0i80D9Ki9DNdZX5YgiOsCliA-ImqEp1pBW9VHD0js_AL9XNCNecoEqhUHvtxzMtCmpwomVeBVL4s5kjUmlCUruA-7vvSF62y8lhYwws0vLCGnyNs3OrUFpy54f95S4dok6lh-hdA7w3t0uva6cbd3xoRiCYUvviGYwWHSmiK8_G029K56db9vsUx37b4CpjFkA9Za4BAmLgNT-D6zZFsiuvxRcA6-NPf1L0jUw-_HXAv_r_pS3J_cuN4RWaHZyP9GlYbw-KNGb1_AJAwM00 |
| linkProvider | Directory of Open Access Journals |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Efficacy%2C+safety+and+dose+selection+of+AZD3759+in+patients+with%C2%A0untreated+EGFR-mutated+non-small-cell+lung+cancer+and%C2%A0central+nervous+system+metastases+in+China+%28CTONG1702-Arm+8%29%3A+a+multi-center%2C+single-arm%2C+phase+2+trial&rft.jtitle=EClinicalMedicine&rft.au=Maggie+Liu%2C+Si-Yang&rft.au=Dong%2C+Xiao-Rong&rft.au=Wang%2C+Zhen&rft.au=Du%2C+Yingying&rft.date=2023-10-01&rft.pub=Elsevier&rft.eissn=2589-5370&rft.volume=64&rft_id=info:doi/10.1016%2Fj.eclinm.2023.102238&rft.externalDocID=PMC10541475 |
| thumbnail_m | http://utb.summon.serialssolutions.com/2.0.0/image/custom?url=https%3A%2F%2Fcdn.clinicalkey.com%2Fck-thumbnails%2F25895370%2FS2589537023X00091%2Fcov150h.gif |