Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial

Song, Zhengbo; Li, Yuping; Chen, Shi-Qing; Ying, Shenpeng; Xu, Shuguang; Huang, Jianjin; Wu, Dan; Lv, Dongqing; Bei, Ting; Liu, Shuxun; Huang, Xiaoping; Xie, Conghua; Wu, Xiaoyu; Fu, Jianfei; Feng, Hao; Wang, Wenxian; Xu, C.; Gao, Chan; Cai, Shangli; Lü, Shun; Zhang, Yiping

doi:10.1186/s12916-022-02245-z

Cited by 37 publications

(42 citation statements)

References 38 publications

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“… 20 Clinical trials also have shown that pyrotinib exhibited high efficacy in NSCLC patients harboring activating HER2 mutations. 21 , 22 Therefore, pyrotinib therapy was considered as an option for the late-line treatment in HER2 mutant cancer patients. Large clinical trials should be conducted to verify the treatment efficacy of pyrotinib in HER2 amplified or mutant cancers.…”

Section: Discussionmentioning

confidence: 99%

Response to Pyrotinib in a Patient with Metastatic Bladder Urothelial Carcinoma Harboring HER2 V842I Mutation: A Case Report

Li¹,

Liu²,

Liu³

et al. 2022

CMAR

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Background The highest incidence of human epidermal growth factor receptor 2 (HER2) mutations has been observed in bladder cancer (BC). However, the function of HER2 mutation in tumor progression and metastasis remains unclear. Currently, no responses to the pan-HER kinase inhibitor were observed in HER2-mutant BC. Case Presentation We described a patient with metastatic bladder urothelial carcinoma (BUC) carrying a HER2 V842I mutation both in circulating tumor DNA (ctDNA) and biopsy sample. The patient was then treated with a HER2 tyrosine kinase inhibitor, pyrotinib, and responded well. However, the targeting treatment was terminated due to G3 diarrhea. Reduced dose of pyrotinib was later added to late-line treatment, the patient’s tumor again responded with a significant decrease in CA199. Conclusion This is the first reported case of HER2 V842I mutation successfully treated with pyrotinib in BUC, suggesting pyrotinib therapy might serve as a therapeutic option for BUC patients harboring HER2 activating mutation.

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Section: Discussionmentioning

confidence: 99%

Response to Pyrotinib in a Patient with Metastatic Bladder Urothelial Carcinoma Harboring HER2 V842I Mutation: A Case Report

Li¹,

Liu²,

Liu³

et al. 2022

CMAR

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“…Afatinib exposure and brain metastases at baseline had no effect on ORR, PFS, or OS. As the illness progressed, the loss of HER2 mutations and the development of amplification in EGFR and HER2 were discovered [ 106 ].…”

Section: Molecular Targetsmentioning

confidence: 99%

Biomarker-Targeted Therapies in Non–Small Cell Lung Cancer: Current Status and Perspectives

Guo

Zhang

Qin

et al. 2022

Cells

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Non-small-cell lung cancer (NSCLC) is one of the most common malignancies and the leading causes of cancer-related death worldwide. Despite many therapeutic advances in the past decade, NSCLC remains an incurable disease for the majority of patients. Molecular targeted therapies and immunotherapies have significantly improved the prognosis of NSCLC. However, the vast majority of advanced NSCLC develop resistance to current therapies and eventually progress. In this review, we discuss current and potential therapies for NSCLC, focusing on targeted therapies and immunotherapies. We highlight the future role of metabolic therapies and combination therapies in NSCLC.

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“…Preclinical and phase I clinical data from breast cancer indicate that pyrotinib can irreversibly inhibit multiple HER receptors (EGFR/HER1, HER2, and HER4) and HER2 overexpressing cells in vitro and in vivo. Studies have shown a 19–53% ORR and a median PFS of 5–6 months in pretreated HER2 mutant NSCLC, even in patients that received prior HER2 directed therapy [ 30 , 31 , 32 ]. HER2 mutant patients with non-exon 20 mutations had an ORR comparable to exon 20 mutations [ 32 ].…”

Section: Treatment Of Her2-altered Nsclcmentioning

confidence: 99%

“…Studies have shown a 19–53% ORR and a median PFS of 5–6 months in pretreated HER2 mutant NSCLC, even in patients that received prior HER2 directed therapy [ 30 , 31 , 32 ]. HER2 mutant patients with non-exon 20 mutations had an ORR comparable to exon 20 mutations [ 32 ]. Pyrotinib has also been studied in in HER2 amplified NSCLC, demonstrating an ORR of 22.2%, and PFS of 6.3 months.…”

Section: Treatment Of Her2-altered Nsclcmentioning

confidence: 99%

“…The presence of other mutations ( HER2 , EGFR , or TP53) was not associated with ORR, PFS, or OS in HER2 amplified NSCLC [ 33 ]. AEs from pyrotinib included diarrhea, elevated blood creatinine, vomiting, and anemia [ 31 , 32 ]. Pyrotinib is a promising agent for HER2 mutant NSCLC and further investigation is in progress in clinical trials.…”

Section: Treatment Of Her2-altered Nsclcmentioning

confidence: 99%

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HER2 in Non-Small Cell Lung Cancer: A Review of Emerging Therapies

Merkhofer

Baik

2022

Cancers

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Human epidermal growth factor receptor 2 (HER2), a member of the ERBB family of tyrosine kinase receptors, has emerged as a therapeutic target of interest for non-small cell lung cancer (NSCLC) in recent years. Activating HER2 alterations in NSCLC include gene mutations, gene amplifications, and protein overexpression. In particular, the HER2 exon 20 mutation is now a well clinically validated biomarker. Currently, there are limited targeted therapies approved for NSCLC patients with HER2 alterations. This remains an unmet clinical need, as HER2 alterations are present in 7–27% of de novo NSCLC and may serve as a resistance mechanism in up to 10% of EGFR mutated NSCLC. There has been an influx of research on antibody–drug conjugates (ADCs), monoclonal antibodies, and tyrosine kinase inhibitors (TKIs) with mixed results. The most promising therapies are ADCs (trastuzumab-deruxtecan) and novel TKIs targeting exon 20 mutations (poziotinib, mobocertinib and pyrotinib); both have resulted in meaningful anti-tumor efficacy in HER2 mutated NSCLC. Future studies on HER2 targeted therapy will need to define the specific HER2 alteration to better select patients who will benefit, particularly for HER2 amplification and overexpression. Given the variety of HER2 targeted drugs, sequencing of these agents and optimizing combination therapies will depend on more mature efficacy data from clinical trials and toxicity profiles. This review highlights the challenges of diagnosing HER2 alterations, summarizes recent progress in novel HER2-targeted agents, and projects next steps in advancing treatment for the thousands of patients with HER2 altered NSCLC.

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Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial

Cited by 37 publications

References 38 publications

Response to Pyrotinib in a Patient with Metastatic Bladder Urothelial Carcinoma Harboring HER2 V842I Mutation: A Case Report

Response to Pyrotinib in a Patient with Metastatic Bladder Urothelial Carcinoma Harboring HER2 V842I Mutation: A Case Report

Biomarker-Targeted Therapies in Non–Small Cell Lung Cancer: Current Status and Perspectives

HER2 in Non-Small Cell Lung Cancer: A Review of Emerging Therapies

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