Targeting HER2 genomic alterations in non-small cell lung cancer

Zeng, Jie; Ma, Weijie; Young, Richard B.; Li, Tianhong

doi:10.1016/j.jncc.2021.04.001

Cited by 18 publications

(15 citation statements)

References 125 publications

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“…15 The highest incidence occurs in bladder cancer (9%-18%), followed by uterine cervix (6%), colorectal (5%-8%), lung (2%-4%), and breast cancer (3%-5%). 3,4,14,[16][17][18][19][20][21] For patients with lung cancer, an increased risk of these variants has also been noted in adenocarcinoma, 14 nonsmokers, women, and persons of Asian descent. 22 Patients with NSCLC harboring HER2 mutations have a worse prognosis than those who do not, as well as worse survival than those with other mutations.…”

Section: Discussionmentioning

confidence: 99%

“…22 Patients with NSCLC harboring HER2 mutations have a worse prognosis than those who do not, as well as worse survival than those with other mutations. 20,23 Use of TKIs has improved survival, 20,23 though response rates have been in the range of 25% to 30% and median duration of responses with TKIs have only been in the range of 4 to 7 months. 20,24,25 The utility of TKIs has been shown to vary with the identity of the specific variant, 26 as well as with which TKI was used, with poziotinib and pyrotinib showing suggestively higher response rates than neratinib, dacomitinib, and afatinib.…”

Section: Discussionmentioning

confidence: 99%

“…20,23 Use of TKIs has improved survival, 20,23 though response rates have been in the range of 25% to 30% and median duration of responses with TKIs have only been in the range of 4 to 7 months. 20,24,25 The utility of TKIs has been shown to vary with the identity of the specific variant, 26 as well as with which TKI was used, with poziotinib and pyrotinib showing suggestively higher response rates than neratinib, dacomitinib, and afatinib. 25 In the SUMMIT trial, a basket trial utilizing neratinib for HER2-mutant cancers, patients with cervical cancer (n55) had an objective response rate (ORR) of 20% at 6 months and a median progression-free survival (mPFS) of 20.1 months.…”

Section: Discussionmentioning

confidence: 99%

“…Gow et al 74 showed sensitivity to afatinib in vitro, and multiple patients have had significant responses to this TKI, with some lasting 1 to 2 years. 20,74,75 Additionally, 4 of 6 patients were reported to have objective responses to pyrotinib, 20,76 and 2 patients with this variant have experienced response to dacomitinib. 77 We are unaware of any prior reports of treatment of this variant with tucatinib.…”

Section: Discussionmentioning

confidence: 99%

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Response of Leptomeningeal Metastasis of Breast Cancer With a HER2/neu Activating Variant to Tucatinib: A Case Report

Yan

Rinn

Kullnat

et al. 2022

Journal of the National Comprehensive Cancer Network

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Metastatic breast cancer demonstrates HER2/neu amplification approximately 15% of the time. However, HER2 mutations, which often stimulate tumor growth, occur in only 3% to 5% of patients, and are seen more frequently in metastatic versus primary tumors. They are more frequent in lobular carcinoma, including triple-negative lobular cancer. Many of these variants are resistant to trastuzumab and lapatinib. However, neratinib can be efficacious, and recent data suggest that antibody–drug conjugates (ADCs) such as ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan may also be helpful. Laboratory and clinical data raise the possibility that simultaneous treatment with ADCs plus neratinib may be even more efficacious. Tucatinib, which has demonstrated significant activity in the central nervous system, has also been shown in vitro to be active against a number of these HER2 variants. This report describes a patient with metastatic estrogen receptor–positive, HER2-nonamplified breast cancer with an activating HER2 mutation whose tumor became resistant to neratinib as well as capecitabine, but whose subsequent leptomeningeal disease had a dramatically successful response to tucatinib plus capecitabine. As the frequency of HER2 mutations increases during the evolution of metastatic breast cancer, it is important to obtain genomic evaluation on these tumors with either repeat tissue or liquid biopsy as they progress over time.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Response of Leptomeningeal Metastasis of Breast Cancer With a HER2/neu Activating Variant to Tucatinib: A Case Report

Yan

Rinn

Kullnat

et al. 2022

Journal of the National Comprehensive Cancer Network

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“…However, after receiving WBRT, cognitive dysfunction will lead to a decrease in the quality of life. With the application of a tyrosine kinase inhibitor (TKI), the survival of NSCLC patients with brain metastasis has been signifcantly prolonged, with a median overall survival (OS) of about 14.8 months [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

The Efficacy and Safety of Afatinib in Non-Small Cell Lung Cancer Patients with Brain Metastasis: A Meta-Analysis

Jin

Liang

et al. 2023

Journal of Oncology

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Aim. The aim of this study is to evaluate the efficacy and safety of afatinib in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastasis based on meta-analysis. Methods. Related literatures were searched in the following databases: EMbase, PubMed, China Knowledge Network (CNKI), Wanfang, Weipu, Google Scholar, the China Biomedical Literature Service System, and other databases. Clinical trials and observational studies that met the requirements were selected for meta-analysis using Revman 5.3. The hazard ratio (HR) was used as an indicator of the impact of afatinib. Results. A total of 142 related literatures were acquired, but after screening, five literatures were selected for data extraction. The following indices were compared: the progression-free survival (PFS), overall survival (OS), and common adverse reactions (ARs) of grade 3 and above. A total of 448 patients with brain metastases were included and were divided into two groups: the control group (no afatinib treatment, with chemotherapy alone and the first-generation EGFR-TKIs) and the afatinib group. The results showed that afatinib could improve PFS (HR: 0.58, 95% CI: 0.39–0.85, P < 0.05 ) and ORR (OR = 2.86, 95% CI: 1.45–2.57, P < 0.05 ), but had no benefit on OS (HR: 1.13, 95% CI: 0.15–8.75, P > 0.05 ) and DCR (OR = 2.87, 95% CI: 0.97–8.48, P > 0.05 ). For the safety of afatinib, the incidence of grade-3-and-above ARs was low (HR: 0.01, 95% CI: 0.00–0.02, P < 0.05 ). Conclusion. Afatinib improves the survival of NSCLC patients with brain metastases and shows satisfactory safety.

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Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancer

Lin,

Ho,

Hsu

et al. 2023

Cancer Medicine

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IntroductionAccording to current International Association for the Study of Lung Cancer guideline, physicians may first use plasma cell‐free DNA (cfDNA) methods to identify epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)‐resistant mechanisms (liquid rebiopsy) for lung cancer. Tissue rebiopsy is recommended if the plasma result is negative. However, this approach has not been evaluated prospectively using next‐generation sequencing (NGS).MethodsWe prospectively enrolled patients with lung cancer with first‐line EGFR‐TKI resistance who underwent tissue rebiopsy. The rebiopsied tissues and cfDNA were sequenced using targeted NGS, ACTDrug®+, and ACTMonitor®Lung simultaneously. The clinicopathological characteristics and treatment outcomes were analyzed.ResultsTotally, 86 patients were enrolled. Twenty‐six (30%) underwent tissue biopsy but the specimens were inadequate for NGS. Among the 60 patients with paired tissue and liquid rebiopsies, two‐thirds (40/60) may still be targetable. T790M mutations were found in 29, including 14 (48%) only from tissue and 5 (17%) only from cfDNA. Twenty‐four of them were treated with osimertinib, and progression‐free survival was longer in patients without detectable T790M in cfDNA than in patients with detectable T790M in cfDNA (p = 0.02). For the 31 T790M‐negative patients, there were six with mesenchymal–epithelial transition factor (MET) amplifications, four with ERBB2 amplifications, and one with CCDC6‐RET fusion. One with MET amplification and one with ERBB2 amplification responded to subsequent MET and ERBB2 targeting agents respectively.ConclusionsNGS after EGFR‐TKI resistance may detect targetable drivers besides T790M. To do either liquid or tissue NGS only could miss patients with T790M. To do tissue and liquid NGS in parallel after EGFR‐TKI resistance may find more patients with targetable cancers.

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Targeting HER2 genomic alterations in non-small cell lung cancer

Cited by 18 publications

References 125 publications

Response of Leptomeningeal Metastasis of Breast Cancer With a HER2/neu Activating Variant to Tucatinib: A Case Report

Response of Leptomeningeal Metastasis of Breast Cancer With a HER2/neu Activating Variant to Tucatinib: A Case Report

The Efficacy and Safety of Afatinib in Non-Small Cell Lung Cancer Patients with Brain Metastasis: A Meta-Analysis

Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancer

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