Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC

Baraibar, Iosune; Mezquita, Laura; Gil‐Bazo, Ignacio; Planchard, David

doi:10.1016/j.critrevonc.2020.102906

Cited by 53 publications

(50 citation statements)

References 95 publications

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“…In the present real-world retrospective cohort, although all patients had the same somatic gene mutation and similar clinical characteristics, their treatment regimens were diverse. For targeted therapy in HER2 exon 20 insertion, in vitro cell-line study demonstrated that the most common YVMA insertion is sensitive to only neratinib, poziotinib, and pyrotinib (24,25). In the clinical setting, targeted therapy is the National Comprehensive Cancer Network (NCCN) guideline-recommended treatment for HER2 mutation (4).…”

Section: Discussionmentioning

confidence: 99%

“…A mechanistic explanation is yet to be established but may implicate intratumoral heterogeneity and lower HER2 expression in HER2-mutant NSCLC compared with in HER2-amplified breast cancer (24). Theraies for HER2mutant NSCLC is under active development, among which the most promising include reversible or irreversible anti-HER2 TKIs and antibody-drug conjugates (ADCs) that target HER2 alone or along with EGFR (25). Patients harboring a HER2 TMD mutations were reported to respond to HER2 tyrosine kinase inhibitor (TKI), lapatinib, and afatinib in case reports (15,26); and to the antibody-drug conjugate, adotrastuzumab emtansine (TDM-1) in a basket trial (9).…”

Section: Introductionmentioning

confidence: 99%

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HER2 transmembrane domain mutation: comprehensive characteristics and real-world evidence of treatment response in Chinese lung adenocarcinoma

Jia¹,

Xing²,

Li³

et al. 2021

Transl Lung Cancer Res

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Background: HER2 transmembrane domain (TMD) mutation has been reported as a rare driver mutation associated with advanced stage disease and a poor prognosis in patients with lung adenocarcinoma (LUAD).We aimed to comprehensively profile the genetic landscape and treatment response information of HER2 TMD-mutant LUAD.Methods: An in-house database of 7,812 LUAD patients was screened for mutation prevalence. A multi-center cohort of 16 HER2 V659E-mutant patients and an external cohort of 38 HER2-mutant patients from cBioPortal with overall survival (OS) data were analyzed. Eight patients from the in-house cohort were included in the real-world study of treatment response. Molecular docking simulation and binding affinity prediction were performed.Results: In Chinese LUAD, the prevalence of HER2 TMD mutation was 0.18% (14/7,812), and 0.14% (11/7,812) for the HER2 V659E mutation. The most recurrent co-alteration was TP53 mutation (n=4, 25%) and HER2 amplification (n=2, 12.5%). TMD-mutant patients were diagnosed at more advance stages (P<0.001) and had poorer OS (median OS 10.0 vs. 61.6 months, HR =7.9, 95% CI: 1.0-61.0, P<0.001) than non-TMD mutations. The overall response rate of targeted therapy, chemo-based therapy, and immunotherapy was 57.1%, 22.2%, and 0%, respectively. We postulated to challenge the resistance 1384 Jia et al. HER2 TMD mutation in NSCLC

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HER2 transmembrane domain mutation: comprehensive characteristics and real-world evidence of treatment response in Chinese lung adenocarcinoma

Jia¹,

Xing²,

Li³

et al. 2021

Transl Lung Cancer Res

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“…Several therapeutic medications targeting HER2 mutations have been developed for lung cancer [234][235][236][237][238][239][240][241][242]. Notably, it was recently reported that trastuzumab deruxtecan achieved a clinically significant tumor response in patients with HER2-mutant-advanced NS-NSCLC whose disease had progressed following one or more previous systemic therapies (chemotherapy or immunotherapy with immune checkpoint inhibitors against PD-1/PD-L1) [237,240] Thus, the search for these mutations either with tissue or cytological samples, or liquid biopsies, may soon become indispensable, too, at diagnosis of advancedstage NS-NSCLC.…”

Section: Her2 Mutationsmentioning

confidence: 99%

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

Hofman

2021

JMP

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The discovery and clinical validation of biomarkers predictive of the response of non-squamous non-small-cell lung carcinomas (NS-NSCLC) to therapeutic strategies continue to provide new data. The evaluation of novel treatments is based on molecular analyses aimed at determining their efficacy. These tests are increasing in number, but the tissue specimens are smaller and smaller and/or can have few tumor cells. Indeed, in addition to tissue samples, complementary cytological and/or blood samples can also give access to these biomarkers. To date, it is recommended and necessary to look for the status of five genomic molecular biomarkers (EGFR, ALK, ROS1, BRAFV600, NTRK) and of a protein biomarker (PD-L1). However, the short- and more or less long-term emergence of new targeted treatments of genomic alterations on RET and MET, but also on others’ genomic alteration, notably on KRAS, HER2, NRG1, SMARCA4, and NUT, have made cellular and blood samples essential for molecular testing. The aim of this review is to present the interest in using cytological and/or liquid biopsies as complementary biological material, or as an alternative to tissue specimens, for detection at diagnosis of new predictive biomarkers of NS-NSCLC.

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“…A T790M mutant patient treated with olmutinib acquired the C797S mutation suggesting that the mechanism of action of olmutinib is similar to osimertinib [108]. Several other small molecule EGFR inhibitors have also been synthesized and they are reviewed elsewhere [109][110][111][112].…”

Section: Epidermal Growth Factor Receptor (Egfr)mentioning

confidence: 99%

Secondary Resistant Mutations to Small Molecule Inhibitors in Cancer Cells

Hamid

Petreaca

2020

Cancers

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Secondary resistant mutations in cancer cells arise in response to certain small molecule inhibitors. These mutations inevitably cause recurrence and often progression to a more aggressive form. Resistant mutations may manifest in various forms. For example, some mutations decrease or abrogate the affinity of the drug for the protein. Others restore the function of the enzyme even in the presence of the inhibitor. In some cases, resistance is acquired through activation of a parallel pathway which bypasses the function of the drug targeted pathway. The Catalogue of Somatic Mutations in Cancer (COSMIC) produced a compendium of resistant mutations to small molecule inhibitors reported in the literature. Here, we build on these data and provide a comprehensive review of resistant mutations in cancers. We also discuss mechanistic parallels of resistance.

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Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC

Cited by 53 publications

References 95 publications

HER2 transmembrane domain mutation: comprehensive characteristics and real-world evidence of treatment response in Chinese lung adenocarcinoma

HER2 transmembrane domain mutation: comprehensive characteristics and real-world evidence of treatment response in Chinese lung adenocarcinoma

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

Secondary Resistant Mutations to Small Molecule Inhibitors in Cancer Cells

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