trastuzumab biosimilar

In patients with de novo MBC, high EGF expression was associated with a non-significant prolongation of TTP (HR=0.52, P=0.080) and significantly longer survival (HR=0.40, P=0.020). The present study examined clinical and biological implications of specific genes and it was concluded that their expression has an impact on the outcome of trastuzumab-treated patients with MBC.

A trend towards longer progression free survival (PFS) was detected univariately for patients with HER2-negative tumors and high expression of VEGFR2, (HR=0.60, p=0.059). VEGFR1 and VEGFR2 seem to have significant prognostic value in BC patients with metastatic disease treated with trastuzumab-based regimens.

Here, we demonstrate that α-amanitin-conjugated trastuzumab (T-Ama) potentiated the HER2-targeted therapy and exhibited superior efficacy in treating HER2-low breast cancer with 17p loss. Moreover, treatment with T-Ama induced immunogenic cell death in breast cancer cells and, thereby, delivered greater efficacy in combination with immune checkpoint blockade therapy in preclinical HER2-low breast cancer models. Collectively, 17p loss not only drives breast tumorigenesis but also confers therapeutic vulnerabilities that may be used to develop targeted precision immunotherapy.

The data indicated the apparent dual role of trastuzumab as an antagonist and an agonist. The molecular details of the simulation provide an atomic level description and molecular insight into the action of HER2-targeted antibody therapeutics.

Prolonged treatments (6 months or more) were observed in at least 17% of cases. The efficacy of T-DM1 after a previous pertuzumab treatment is lower than if pertuzumab is not given, although prolonged responses are observed in this setting.

Two diagnostic models, created by combining clinicopathological factors and ITH indicators, showed excellent potential diagnostic ability for pCR (mean gene copy number and protein category CV; AUC = 0.837, proportion of gene- and protein-positive tumor cells; AUC = 0.831). HER2 ITH quantified by GPA is a potential predictive indicator for efficacy of HER2-targeted treatment.

In addition, enhanced miR-567 could be packaged into exosomes, incorporated into receipt cells, suppressing autophagy and reversed chemoresistance by targeting ATG5. To conclude, exosomal miR-567 plays a key role in reversing trastuzumab resistance via regulating autophagy, indicating it may be a promising therapeutic target and prognostic indicator for breast cancer patients.

As a result, they do not benefit from hormonal or trastuzumab-based therapy. More malignant tumors of the breast are more often ER and PR negative in both humans and dogs. Promising breast cancer biomarkers in both humans and canines are cancer-associated stroma (CAS), circulating tumor cells and tumor DNA (ctDNA), exosomes and miRNAs, and metabolites.

Report: A 48-year-old female patient underwent cancer treatment for T4N1M0 clinical cancer for 2 years, requiring a total left mastectomy and chemotherapy that included anthracycline (Doxorubicin), obtaining a complete response. After one year, a left sentinel axillary lymph node biopsy was performed, which showed a positive HER-2 marker in immunohistochemistry, treated with Capecitabine and Trastuzumab...Classified as intermediate risk, she started Induction treatment with Tretinoin (ATRA) and Daunorubicin (dose corrected by previous use of this class of medication)... In the report, the mechanisms described in the literature, which relate breast cancer to AML, are present for the rare and early manifestation of hematopoietic disease.

Drugs with the highest amount of clinical trials in phases 3 and 4 were paclitaxel, docetaxel, trastuzumab, tamoxifen and doxorubicin. Lastly, we collected ~3,500 somatic and germline oncogenic variants associated with 50 essential genes, which in turn had therapeutic connectivity with 73 drugs. In conclusion, the OncoOmics strategy reveals essential genes capable of accelerating the development of targeted therapies for precision oncology.

NCT-547 was an effective inhibitor of tumor growth and angiogenesis, and no toxic outcomes were found in initial hepatic and renal analysis. Our findings suggest that NCT-547 may have applications in addressing trastuzumab resistance in HER2-positive breast cancer.

Treatment of human epithelial growth factor receptor 2 (HER2)-positive breast cancer has rapidly evolved over the past decades with the addition of trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1). Heterogeneous evidence from cost-effectiveness studies on the use of targeted directed agents for HER2-positive mBC across the world caution against cross-country comparisons of the value of such treatments. It also militates in favor of the production and use of cost-effectiveness analyses for local rather than global decision-making, thus ensuring that economic evaluations reflect the needs of local decision-makers and populations for which they are devised.

In a Trastuzumab-resistant patient-derived tumor xenograft model GA0060, GB235 plus Trastuzumab reversed the resistance to Trastuzumab monotherapy. Because GB235 showed a different working mechanism with Pertuzumab and Trastuzumab, these agents can be considered complementary therapy against HER2 overexpression tumors.

HER2 negative conversion is mostly associated with chemotherapy and trastuzumab and is stil considered as a bad prognostic factor. Awareness of this mechanisms is important to decide the best therapy options especially in metastatic lesions.

HER2 negative conversion is mostly associated with chemotherapy and trastuzumab and is stil considered as a bad prognostic factor. Awareness of this mechanisms is important to decide the best therapy options especially in metastatic lesions.

HER2 negative conversion is mostly associated with chemotherapy and trastuzumab and is stil considered as a bad prognostic factor. Awareness of this mechanisms is important to decide the best therapy options especially in metastatic lesions.

Although amplification of the gene encoding human epidermal growth factor receptor 2 (HER2) is used as an indicator for response to trastuzumab, the reported response rate is low, and few patients with gastric cancer (GC) benefit from this individualized therapy. Due to the highly heterogeneous aspect of GC, at least 3-4 slides should be assessed by IHC, before considering a tumor to be HER2-negative. In cases with small 3+ foci representing less than 5% of tumor and in equivocal (2+) cases, FISH analysis remains the gold standard method.

Advanced gastric cancer is treated with sequential lines of chemotherapy, starting with a platinum and fluoropyrimidine doublet in the first line; median survival is less than 1 year. Targeted therapies licensed to treat gastric cancer include trastuzumab (HER2-positive patients first line), ramucirumab (anti-angiogenic second line), and nivolumab or pembrolizumab (anti-PD-1 third line).

GE-226 is a radiolabelled Affibody® tracer which binds to the HER2 receptor with high affinity at a different epitope than trastuzumab. Conclusions [18F]GE-226 imaging is well tolerated and shows promise for imaging of HER2 positive breast cancer. Further studies with this agent are now planned.

Secondary outcomes were progression-free survival (PFS) for each line of treatment and for each type of treatment (trastuzumab [T], pertuzumab [P], lapatinib [L] and trastuzumab emtansine [T-DM1]). In this retrospective study of patients from a real-world setting, anti-HER2 therapies offered similar OS between HER2-positive mBC patients with recurrent disease and with de novo metastatic disease. Median PFS are also equivalent between groups, with durations in the range of the PFS reported in major RCTs.

HER2+ breast cancer treated with trastuzumab prior to fractionated radiation synergistically increases efficacy of radiotherapy in vitro and in vivo . [ 18 F]-FMISO-PET imaging has potential to identify in vivo response to combination therapies and better understand changes in the tumor microenvironment to guide combination therapy.

Prognostic superiority of YAP/TAZ expression depended on hormone receptor status. Cases with synchronous over-expression of YAP/TAZ and HER3 suffered poor survival, which revealed the potential effect of YAP/TAZ-HER2/HER3 crosstalk in prognosis of HER2-positive patients.

PACAP or NRG-1 increased the proliferation of NSCLC cells, whereas PACAP(6-38), gefitinib, trastuzumab, or mAb3481 inhibited proliferation. The results indicate that PAC1 regulates the proliferation of NSCLC cells as a result of transactivation of the EGFR, HER2, and HER3.

Results of studies indicate similar efficacy between the two routes of administration. The higher rates of adverse events for SC administration were mainly attributable to injection site-related events. The clinical decision of whether to administer trastuzumab SC or IV requires the consideration of several factors and should be determined individually.

We present a combinatorial PIT approach for targeting BC expressing EGFR and HER2, using PA- labeled panitumumab (pan) and trastuzumab (tra), respectively. Combination PIT is a promising approach for treating BC with low/moderate expression of surface receptors. In addition, given the molecular heterogeneity of bladder cancer, targeting more than one surface receptor may allow for more effective cell death across different bladder tumors.

Patients with low-risk tumors now experience excellent long-term outcomes and reduced toxicity after de-escalated adjuvant therapy, and patients with high-risk residual disease after neoadjuvant systemic therapy have had a significant decrease in the risk for disease recurrence with the escalation of adjuvant therapy, including the use of trastuzumab emtansine (also known as T-DM1). We also discuss areas of ongoing clinical uncertainty, including how disease heterogeneity and hormone receptor status affect the selection of treatments and the selection of patients for chemotherapy-free approaches. Finally, we review ongoing areas of active investigation and unmet clinical needs in this patient population.

The addition of targeted therapies may not significantly increase breast conserving surgery rates (RR, 1.04; 95% CI, 0.97-1.12). The addition of targeted therapies, especially trastuzumab for patients with HER2-positive breast cancer and bevacizumab for patients with HER2-negative breast cancer significantly increased pathologic complete response, overall response, and clinical complete response but not breast conserving surgery rates.

Frequent heterogeneity of HER2 protein expression combined with the possibility of a spatially more heterogenous sampling of endometrial cavity in biopsies and curettings, and the potential differences in specimen handling/fixation between the 2 specimen types may explain our findings. HER2 testing of multiple specimens may help identify a greater proportion of patients eligible for targeted trastuzumab therapy and should be taken into account in future efforts of developing endometrial cancer-specific HER2 testing algorithm.

HER2 heterogeneity in advanced gastric cancer is associated with a poor prognosis and affects the clinical efficacy of trastuzumab. In both cases, TP53 mutations were observed in both HER2-positive and HER2-negative areas, whereas many of the potential driver and passenger mutations differed between HER2-positive and HER2-negative areas. Overall, our findings demonstrated that HER2 heterogeneous gastric cancer exhibited intratumoral genetic heterogeneity in other cancer-related genes and that the molecular mechanisms could differ between HER2-positive and -negative areas.

Actionable receptor tyrosine kinase alterations assayed within a genomic context with therapeutic implications remain limited to HER2 amplification in gastroesophageal adenocarcinomas (GEA). Composite biomarkers and heterogeneity assessment are critical in optimizing patients selected for targeted therapies in GEA. Comprehensive genomic profiling in FGFR2-altered GEA parallels the heterogeneity findings in HER2-amplified GEA and adds support to the utility of genomic profiling in advanced gastroesophageal adenocarcinomas.

TR-PIN functionalization with cetuximab, holo-transferrin, and trastuzumab conferred specificity for epidermal growth factor receptor (EGFR), transferrin receptor (TfR), and human epidermal growth factor receptor 2 (HER-2), respectively. Photodestruction using TR-PINs was significantly higher than the monotargeted Cet-PINs in heterocellular 3D in vitro models of heterogeneous pancreatic ductal adenocarcinoma (PDAC; MIA PaCa-2 cells) and heterogeneous head and neck squamous cell carcinoma (HNSCC, SCC9 cells) containing low-EGFR-expressing T47D (high TfR) or SKOV-3 (high HER-2) cells. Through their capacity for multiple tumor target recognition, TR-PINs can serve as a unique and amenable platform for the effective photodynamic eradication of diverse tumor subpopulations in heterogeneous cancers to mitigate escape for more complete and durable treatment responses.

Through the use data of the different formulations available for trastuzumab and taking into account the prescriptive appropriateness (and patient preferences), it has been possible to identify a SSR scenario of economic convenience due to the greater use of the biosimilar.

Several pCR predictors, such as PAM50, Integrative Cluster (IntClust), mutations in PI3KCA, or the Trastuzumab Risk model (TRAR), are useful molecular tools for estimating response to treatment and are prognostic. This dynamic nature of the determinants of response to BC NAC, together with the extensive heterogeneity of BC, raises the need to discern the individual and subtype-specific determinants of resistance. Moreover, refining the current approaches for a comprehensive monitoring of tumor evolution during treatment, RD, and eventual recurrences is essential for identifying new actionable alterations and the integral best management of the disease.

Funding: Roche. Clinical trial identification: NCT03829306.

In particular, we identified high ERBB2 mRNA in a patient with HER2+ advanced gastric cancer who achieved a long-lasting partial response to T-DM1. Our study demonstrates that the heterogeneity in response to T-DM1 is partly explained by ERBB2 levels and provides a clinically applicable assay to be tested in future clinical trials of breast cancer and other cancer types.

We emphasize the importance of regular tissue confirmation of predictive markers in progressive tumorous disease even if our presented case is not unequivocally a "conversion case". Tumor subtype is determined according to algorithms and definitions published in guidelines, nevertheless, use of different guidelines may lead to controversial interpretation in cases where HER2 genetic heterogeneity is present. Furthermore, we suggest that seronegative, aseptic intracranial fluid effusion after the removal of a brain metastasis may possibly be a side effect of trastuzumab.

This protocol can provide high contrast images of tumors expressing ER or HER2 within 3 days from injection of 4FMFES to final scan of Zr-T and, hence, provides a basis for future dual-tracer combinations that include antibodies.

Systemic chemotherapy regimens have changed greatly, especially since the introduction of trastuzumab. Recently, immune checkpoint blockade has been well developed as a promising anticancer strategy. This review outlines the currently available information on clinically tested molecular targeted drugs and immune checkpoint inhibitors for AGC to provide support for decision-making in clinical practice.

NK-92 cells that were engineered to express FcγRIII (CD16) mediated antibody-dependent cellular cytotoxicity (ADCC) selectively against HER2+ cells upon addition of Herceptin (trastuzumab). Mass proteomic analysis of the two effector cell lines suggested differential changes in adhesion, exocytosis, metabolism, transport and activation of upstream regulators and cytotoxicity mediators, which can be utilized to regulate specific functionalities of NK-92 cells in future. These results suggest that this semi-automated single cell assay can reveal the variability and functional potency of NK cells and may be used to optimize immunotherapeutic efficacy for preclinical analyses.

Based on these results, we suggest to give the addition of trastuzumab to HER-2 positive patients instead of changing the chemotherapy regimen and proceeding to surgery instead of further chemotherapy once patients have PD during NACT. Given that some similar characteristics exist between PD and pCR patients, more studies to identify novel molecular markers to predict disease response to NACT should be performed.