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

Maggie Liu, Si-Yang; Dong, Xiao-Rong; Wang, Zhen; Du, Yingying; Cui, Jiu-Wei; Chu, Qian; Xu, Bing-Fei; Zheng, Ming-Ying; Deng, Jia-Yi; Lu, Chang; Wei, Xue-Wu; Li, Yang-Si; Zheng, Mei-Mei; Yang, Ming-Yi; Huang, Jie; Li, Anna; Bai, Xiao-Yan; Sun, Yue-Li; Xu, Chong-Rui; Wang, Bin-Chao; Chen, Hua-Jun; Yang, Jin-Ji; Yan, Hong-Hong; Zhong, Wen-Zhao; Zhou, Qing; Wu, Yi-Long

doi:10.1016/j.eclinm.2023.102238

Cited by 3 publications

(4 citation statements)

References 26 publications

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“…She achieved PR in both extra‐ and intracranial tumor lesions, developed EGFR T790M mutation after PD on zorifertinib, and finally achieved an OS of more than 65 months. The AEs with zorifertinib were consistent with those reported in phase 1–3 studies and other EGFR‐TKIs 10,12,13 …”

Section: Discussionsupporting

confidence: 81%

“… 10 , 18 In previous studies, first‐line zorifertinib was particularly effective in controlling BM (extracranial PD is the main pattern of PD), and the main acquired resistance mutation was EGFR T790M which is subsequently treatable with third‐generation EGFR‐TKIs, helping to prolong OS of patients; the median OS was 34.1 months in patients subsequently treated with osimertinib in CTONG1702, and is consistent with that of the phase 3 EVEREST study (data on file). 12 , 13 …”

Section: Discussionmentioning

confidence: 99%

“…The AEs with zorifertinib were consistent with those reported in phase 1–3 studies and other EGFR‐TKIs. 10 , 12 , 13 …”

Section: Discussionmentioning

confidence: 99%

“…Zorifertinib (AZD3759), a novel EGFR‐TKI inhibiting mutant EGFR (exon 19del or L858R), is not a substrate of either P‐glycoprotein or breast cancer resistance protein and was designed specifically to improve blood–brain barrier (BBB) penetration 10,11 and to treat EGFR ‐mutant NSCLC patients with BM. In phase 1–3 studies, zorifertinib has shown promising antitumor activity 10,12,13 …”

Section: Introductionmentioning

confidence: 99%

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Long‐term survival of a patient with epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC) and untreated multiple brain metastases treated with zorifertinib: A case report

Li,

Chen,

Wang

et al. 2024

Thoracic Cancer

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Brain metastases (BM) are common in patients with epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC) and confer poor prognoses. Zorifertinib (AZD3759), an EGFR‐tyrosine kinase inhibitor (TKI) with high blood‐brain barrier penetration, has previously demonstrated promising systemic and intracranial antitumor activity in phase 1–3 studies. This is the first report of a patient with EGFR‐mutant (exon 21 L858R) NSCLC and symptomatic untreated multiple BM who achieved a long overall survival (OS) of more than 65 months after sequential treatment with zorifertinib and a third‐generation EGFR‐TKI. This new treatment paradigm offers a new treatment option and deserves further clinical exploration to prolong OS of patients with EGFR‐mutant NSCLC and untreated multiple BM.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

“…The AEs with zorifertinib were consistent with those reported in phase 1–3 studies and other EGFR‐TKIs. 10 , 12 , 13 …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Long‐term survival of a patient with epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC) and untreated multiple brain metastases treated with zorifertinib: A case report

Li,

Chen,

Wang

et al. 2024

Thoracic Cancer

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Treatment Advances in Lung Cancer with Leptomeningeal Metastasis

Meng,

Zhu,

Yang

et al. 2024

CCDT

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Leptomeningeal metastasis (LM) is a serious and often fatal complication in patients with advanced lung cancer, resulting in significant neurological deficits, decreased quality of life, and a poor prognosis. This article summarizes current research advances in treating lung cancer with meningeal metastases, discusses clinical challenges, and explores treatment strategies. Through an extensive review of relevant clinical trial reports and screening of recent conference abstracts, we collected clinical data on treating patients with lung cancer with meningeal metastases to provide an overview of the current research progress. Exciting progress has been made by focusing on specific mutations within lung cancer, including the use of EGFR tyrosine kinase inhibitors or inhibitors for anaplastic lymphoma kinase gene rearrangement, such as osimertinib, alectinib, and lorlatinib. These targeted therapies have shown impressive results in penetrating the central nervous system (CNS). Regarding whole-brain radiotherapy, there is currently some controversy among investigators regarding its effect on survival. Additionally, immune checkpoint inhibitors (ICIs) have demonstrated reliable clinical benefits due to their ability to retain anticancer activity in CNS metastases. Moreover, combination therapy shows promise in providing further treatment possibilities. Considerable progress has been made in the clinical research of lung cancer with LM. However, the sample size of prospective clinical trials investigating LM for lung cancer is still limited, with most reports being retrospective. Developing more effective management protocols for metastatic LM in lung cancer remains an ongoing challenge for the future.

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Dose Optimization of Targeted Therapies for Oncologic Indications

Zettler

2024

Cancers

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Therapeutic advances in oncology in the 21st century have contributed to significant declines in cancer mortality. Notably, targeted therapies comprised the largest proportion of oncology drugs approved by the United States (US) Food and Drug Administration (FDA) over the past 25 years and have become the standard of care for the treatment of many cancers. However, despite the metamorphosis of the therapeutic landscape, some aspects of cancer drug development have remained essentially unchanged. In particular, the dose-finding methodology originally developed for cytotoxic chemotherapy drugs continues to be implemented, even though this approach no longer represents the most appropriate strategy for modern cancer therapies. In recognition of the need to reconsider assumptions, adapt the dose selection process for newer drugs, and design alternative strategies, the FDA has undertaken several initiatives in recent years to address these concerns. These actions include the launch of Project Optimus in 2021 and the issuance of draft guidance for industry on dose optimization of oncology drugs in 2023. Amid this evolving regulatory environment, the present manuscript reviews case studies for six different targeted cancer therapies, highlighting how dose-finding challenges have been managed to date by oncologists, sponsors, and regulators.

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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

Cited by 3 publications

References 26 publications

Long‐term survival of a patient with epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC) and untreated multiple brain metastases treated with zorifertinib: A case report

Long‐term survival of a patient with epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC) and untreated multiple brain metastases treated with zorifertinib: A case report

Treatment Advances in Lung Cancer with Leptomeningeal Metastasis

Dose Optimization of Targeted Therapies for Oncologic Indications

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