HER-2 mutation

Treatment of Ba/F3 or lung cells expressing MDK::ERBB2 with ERBB2 inhibitors (afatinib, poziotinib, tucatinib) blocked phosphorylation of ERBB2 and downstream effectors, and inhibited growth of both cell lines. ERBB2 fusions are rare oncogenic drivers that are candidates for targeted therapy. The subset of recurrent ERBB2 fusions with C-terminal/3' partners may represent an alternative mechanism of fusion oncogenicity.

P2, N=193, Not yet recruiting, Shanghai East Hospital; Shanghai East Hospital

The personalized scoring prediction model constructed based on multiple tumors, ERBB2 miss mutation, CA125 levels, CA153 levels, tumor site, tumor length, and serum ferritin can screen NSCLC patients who may have OLNM.

P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis, and early application of gene sequencing is beneficial for evaluating prognosis.

P2, N=88, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

No copy number-associated variants or structural variations were identified in either lesion. These results suggest that patients with ISMC may benefit from PD-L1 immunotherapy and targeted therapy.

CDK4 high-level copy number increase coexists with other pathogenic mutations in AM. CDK4 appears to be a promising target for AM treatment and is expected to be combined with other targeted therapies.

Patients with NSCLC harboring select AGAs, including EGFR and ALK alterations, have a higher risk for TF, shorter median time to TF, and diminished pathological regression after neoadjuvant ICIs. The suboptimal efficacy of neoadjuvant chemotherapy-sparing, ICI-based regimens in this patient subset underscores the importance of tumor molecular testing prior to initiation of neoadjuvant ICI therapy in patients with resectable NSCLC.

P2, N=152, Completed, Daiichi Sankyo | Active, not recruiting --> Completed

These antibodies as T cell engagers selectively killed a HER2 S310F-driven cancer cell line in vitro, and in vivo as a xenograft. These results validate HER2 ECD mutations as actionable therapeutic targets and offer promising candidates toward clinical development.

Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with HER2-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with HER2-mutant NSCLC receiving platinum-based chemotherapy with ICIs.

P2; Urinary MRD testing after nadofaragene firadenovec induction provided statistically significant prognostication of recurrence among phase 2 trial participants.

In the liquid biopsies, we detected ESR1 mutations in 42 cases (25.9%) and ERBB2 mutations in six cases (3.7%), arguing for a change in therapy to fulvestrant, elacestrant, or neratinib. Furthermore, 17 cases had detectable TP53 mutations, associated with resistance against endocrine therapy. We conclude that liquid biopsy testing is a noninvasive, sensitive, and helpful method to optimize therapeutic decisions in metastatic BC.

The prevalence of lithiasis seems to be higher in Chilean versus US patients with GBC. A similar prevalence of ERBB2 alterations of overall 14% and better OS suggests that a proportion of them could benefit from human epidermal growth factor receptor type 2-targeted therapies. The smaller cohort of Chile, where the disease prevalence is higher, is a reminder and invitation for the need of more robust next-generation sequencing analyses globally.

Nevertheless, disease progression inevitably occurs, limiting osimertinib long-term efficacy...Early phase 1/2 clinical trials are ongoing to elucidate their activity also in the clinical setting. Aim of this review is to provide a state-of-the-art analysis on preclinical development of fourth-generation EGFR-TKIs and promising preliminary clinical data.

P1, N=554, Recruiting, Boehringer Ingelheim | Trial primary completion date: Dec 2025 --> Mar 2026

Ipatasertib+paclitaxel demonstrated more encouraging activity. The tolerability of both regimens was consistent with previous experience.

Notably, EGFR ex20 insertions exhibited greater insertion diversity. Clinical characteristics of EGFR and ERBB2 ex20 NSCLC were similar, characterized by low tumor mutation burden (TMB), a predominant never-smoker population, and a majority of lung adenocarcinoma cases.

P2, N=56, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

This mutation is probably sensitive to tyrosine kinase inhibitory drugs. These results are similar to those in human medicine and to the few data in the literature on canine lung carcinomas; the presence of 12.5% of amplified cases in dogs lays the foundation for future targeted drugs against HER2 alterations.

Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients.

The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

P1, N=396, Active, not recruiting, Jiangsu HengRui Medicine Co., Ltd. | Recruiting --> Active, not recruiting | N=226 --> 396 | Trial completion date: Dec 2023 --> Mar 2026 | Trial primary completion date: Dec 2023 --> Dec 2025

Response duration was 12.0 and 9.3 months for patients identified by the ODxT Test and CTAs, respectively, in DESTINY-Lung01. The ODxT Test detected HER2 mutations in NSCLC with high analytical and clinical accuracy and identified HER2m populations with response rates similar to populations identified by CTAs, supporting clinical utility of the ODxT Test to inform treatment decisions for HER2m NSCLC.

No abstract available

P=N/A, N=186, Recruiting, Yongchang Zhang | Trial primary completion date: Jan 2024 --> Jan 2025

P2, N=30, Recruiting, Yongchang Zhang | Trial primary completion date: Dec 2023 --> Dec 2024

Known under low incidence – mutations require research for 0.4% to 1.1 in pulmonary adenocarcinomas, IDH1/2 inhibitors prescription due to high prevalence of lung carcinoma worldwide. Mutations in IDH1/2 gene may be branching drivers leading to lower subclonality evolution with predictable benefit of IDH1/2 inhibitors.The accumulation of more known cases with IDH1/2 mutations is necessary to elucidate clinicopathological characteristics/clinical evolution after target therapy, in order to reforce the new interpretation of malignant tumours postponed survival through conversion of cell cycle.

Massive parallel sequencing and personalized therapeutic targets for personalized mutational status might allow patients with adenosquamous carcinomas to improve survival at the different levels of progression. Adapted criteria in the classification recognized by WHO 2021, which tumoural cellular level sub-classification might be a particular sub-typing with particular outcomes as exemplified in the present mutational exercise. This small series, defined after routine IHC classification correlated with tumoural heterogeneity/clonality previewed for adenosquamous carcinoma.

Oncogenic activation of genes-drivers are responsible for resistance mechanisms either understood has resistance to METtargeted therapies and as primary resistance. Recently it has been reported that PI3K pathway alteration is common in concomitancy with METex14 and believed that confers primary resistance to MET TKI. Early identification of alterations in MET kinase domain at diagnosis, is crucial for understanding progression and resistance mechanism, to develop novel therapies or to design treatment strategies in order to improve patient outcomes.

Our study showed the heterogeneity in PD-L1 expression with respect to major oncogenic drivers in Turkey. KRAS, BRAF, MET mutations and ALK and ROS1 rearrangements were more frequent, while EGFR and HER2 mutations were less frequent compared with the overall PD-L1 expression levels. Molecular testing of non-small cell lung carcinomas (NSCLC) for oncogenic driver mutations has become standard in pathology practice.

To our knowledge, this is the first report showing the efficacy of pembrolizumab in a patient with cholangiocarcinoma harboring both HER2-positive and TMB-H.

Zongertinib potently and selectively blocks HER2, while sparing EGFR, and inhibits the growth of cells dependent on HER2 oncogenic driver events, including HER2-dependent human cancer cells resistant to trastuzumab deruxtecan. Zongertinib displays potent anti-tumor activity in HER2-dependent human NSCLC xenograft models and enhances the activities of antibody-drug conjugates and KRASG12C inhibitors, without causing obvious toxicities. The preclinical efficacy of zongertinib translates in objective responses in patients with HER2-dependent tumors, including cholangiocarcinoma (SDC4-NRG1 fusion) and breast cancer (V777L HER2 mutation) thus supporting the ongoing clinical development of zongertinib.

Elderly age >50 years (OR = 2.6 [CI: 1.3-5.2]; p = .010) and frequent peanut consumption (OR = 2.3 [CI: 1.1-4.9]; p = .030) were independent risk factors for high serum AAA levels. The current study has implications for the prevention of GBC through the reduction of dietary aflatoxin exposure.

This could be of clinical value as a potential therapeutical target concerning emerging therapeutic treatments (antibody conjugates). However, the clinical significance of this expression still needs to be established.

TEs occurred later with EGFR and ALK , while earlier with ROS1 or KRAS with STK11, KEAP1 or SMARCA4 co-mutations compared to those with KRAS mutations alone. $$table_{7740CBC2-774F-48DA-932A-077113E7FED5}$$

TEs occurred later with EGFR and ALK , while earlier with ROS1 or KRAS with STK11, KEAP1 or SMARCA4 co-mutations compared to those with KRAS mutations alone. Cumulative incidence of venous and arterial TEs % 0 6 weeks 6 months 1 year 2 years 3 years Overall 2.8 6 11.7 15.8 21.5 26.2 ALK 5.3 10.7 12 14.8 14.8 17 BRAF 2.1 5.8 12.9 16.3 19.5 27.9 EGFR 2 5.8 10.2 14 17.9 23 HER2 0 3.5 7.2 9.2 19.5 23 KRAS 2.7 5.1 11.3 15.3 22.5 27.1 MET 14 6.8 11.3 21.2 21.2 23.9 27.7 RET 13.3 23.3 33.3 36.6 44.5 50.1 ROS1 12 20 34.2 34.2 45.1 53.3

Our study provides valuable insights into the understanding of age- and ethnic-driven molecular and clinical disparities in breast cancer patients. By unraveling the intricate relationship between genetic alterations and clinical outcomes, we underscore the potential for personalized treatment strategies in BC patients guided by molecular profiles. Nevertheless, further investigations are warranted to elucidate the underlying mechanisms that govern these dynamic processes.

The present results indicate a higher rate of accessibility for MT in breast cancer, and the impact of F1CDx/F1LCDx on treatment decision-making was significant. Prognostic analysis will be performed at the end of the observation period (planned for two years).

Significant associations between ERBB2 alterations and HER2 low-expressing tumors were observed. High prevalence of ERBB2 alterations was observed in some uncommonly tested tumors. Median OS of HER2 low-expressors was better than non-expressors in this heterogenous group.

Our study highlights the variable expression and significance of HER2 testing across multiple solid tumor types, reinforcing the importance of HER2 testing to optimize the utilization of T-Dxd in the real-world setting.