- |||||||||| Kadcyla (ado-trastuzumab emtansine) / Roche, Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca, Perjeta (pertuzumab) / Roche
Journal, BRCA Biomarker, PD(L)-1 Biomarker, IO biomarker, Metastases: Systemic Treatment of Patients With Metastatic Breast Cancer: ASCO Resource-Stratified Guideline. (Pubmed Central) - Jan 11, 2024
It is ASCO's view that healthcare providers and system decision-makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.
- |||||||||| Votrient (pazopanib) / Novartis, BeiGene
Biomarker, Journal, Tumor microenvironment: The role of senescence genes in the treatment, prognosis, and tumor microenvironment of gastric cancer. (Pubmed Central) - Jan 8, 2024
Senescence genes were related to the prognosis, response to chemotherapy drugs, and TME of GC. Our senescence-related risk model could forecast the survival of patients, their response to chemotherapy drugs, and the TME to a certain extent.
- |||||||||| Retrospective data, Journal, Real-world evidence, Real-world, Metastases: Third-line treatment patterns in HER2-positive metastatic breast cancer: a retrospective analysis of real-world data in Canada. (Pubmed Central) - Jan 1, 2024
The absence of a consensus on post-second-line treatment highlights the pressing need for more efficient therapeutic alternatives beyond the currently available options. This study not only offers valuable insights into the present landscape of third-line treatment in Canada but validates the significance and effectiveness of the PMT registry as a tool for generating pan-Canadian real-world evidence in oncology and its capacity to provide information on evolution of therapeutic practices.
- |||||||||| Review, Journal, Metastases: Advances in HER2-Targeted Treatment for Advanced/Metastatic Urothelial Carcinoma. (Pubmed Central) - Dec 29, 2023
In this review, we provided an in-depth overview of the advances in the research regarding HER2-targeted therapy and the role of HER2 in mUC. Furthermore, we also discussed the prospects of potential strategies aimed at overcoming anti-HER2 resistance, and summarize the novel anti-HER2 approaches for the management of mUC used in recent clinical trials.
- |||||||||| Irene (pyrotinib) / Jiangsu Hengrui Pharma, DA 3111 (trastuzumab biosimilar) - Meiji Seika, Dong / A, Herceptin (trastuzumab) / Roche
Retrospective data, Journal, Real-world evidence, Real-world, Metastases: Real-world data of triplet combination of pyrotinib, trastuzumab, and chemotherapy in HER2-positive metastatic breast cancer: a multicenter, retrospective study. (Pubmed Central) - Dec 25, 2023
P
The most prevalent chemotherapies paired with PyroH were capecitabine (36.3%)...Longer previous trastuzumab (?6.37 months) or lapatinib (?10.05 months) therapies could indicate improved PFS, while prior pyrotinib exposure negatively influenced PFS...PyroHC shows promising efficacy and a satisfactory safety profile for treating HER2+ MBC, both as a first-line option and for heavily treated patients, including those with brain metastasis. Our findings suggest the duration and history of anti-HER2 therapy as potential predictors for PyroHC efficacy in advanced settings.
- |||||||||| Sutent (sunitinib) / Pfizer
Journal, PD(L)-1 Biomarker, IO biomarker: Impact of disulfidptosis-associated clusters on breast cancer survival rates and guiding personalized treatment. (Pubmed Central) - Dec 24, 2023
Finally, Immunohistochemistry (IHC) validated the expression of prognostic genes, demonstrating higher levels in tumor tissue compared to normal tissue. Our study has developed an effective disulfidptosis-related prognostic prediction tool for BC and provides personalized guidance for the clinical management and immunotherapy selection of BC patients.
- |||||||||| Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca, Tukysa (tucatinib) / Pfizer, Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
Journal: Novel HER2-targeted therapy to overcome trastuzumab resistance in HER2-amplified gastric cancer. (Pubmed Central) - Dec 24, 2023
Moreover, T-DXd induced the expression of pH2A.X and cPARP and caused cell cycle arrest in the S or G2-M phase in TR cell lines. T-DXd showed promising antitumor activity in both parental and TR cell lines, suggesting that it is a potential candidate for overcoming trastuzumab resistance.
- |||||||||| lapatinib / Generic mfg., erlotinib / Generic mfg., gefitinib / Generic mfg.
Journal: F-Labeled brain-penetrant EGFR tyrosine kinase inhibitors for PET imaging of glioblastoma. (Pubmed Central) - Dec 11, 2023
The radiotracers were produced on an automated synthesis module in 7-8% activity yield with high molar activity. In vivo PET imaging revealed rapid brain uptake in rodents and tumor accumulation in an EGFR-driven orthotopic GBM xenograft model.
- |||||||||| lapatinib / Generic mfg., erlotinib / Generic mfg.
Journal: Different EGF-induced receptor dimer conformations for signaling and internalization. (Pubmed Central) - Dec 10, 2023
These results reveal that the conformation of the intracellular TK dimer, rather than the known EGFR signaling, is critical for EGFR internalization. These results also illustrate clear differences in the mode of action of TK inhibitors on the EGFR and open novel possibilities to control EGFR signaling for cancer treatment.
- |||||||||| Tafinlar (dabrafenib) / Novartis
Trial completion date, Trial primary completion date, Combination therapy, Surgery: Dabrafenib and Lapatinib in Treating Patients With Refractory Thyroid Cancer That Cannot Be Removed by Surgery (clinicaltrials.gov) - Dec 5, 2023
P1, N=21, Active, not recruiting,
These results also illustrate clear differences in the mode of action of TK inhibitors on the EGFR and open novel possibilities to control EGFR signaling for cancer treatment. Trial completion date: Jul 2023 --> Dec 2024 | Trial primary completion date: Jul 2023 --> Dec 2024
- |||||||||| lapatinib / Generic mfg., sorafenib / Generic mfg.
Journal: The role of cytochrome P450 3A4-mediated metabolism in sorafenib and lapatinib hepatotoxicity. (Pubmed Central) - Dec 1, 2023
To our surprise, the data indicate that CYP3A4 increases resistance to sorafenib and lapatinib hepatotoxicity. The results have implications for the mechanism of toxicity of these drugs in patients and underline the importance of selecting an appropriate experimental model.
- |||||||||| Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca, Tukysa (tucatinib) / Seagen
Journal: Multiomics of HER2-low triple-negative breast cancer identifies a receptor tyrosine kinase-relevant subgroup with therapeutic prospects. (Pubmed Central) - Nov 27, 2023
In vitro and in vivo patient-derived xenograft experiments revealed that pretreatment of the TKR subgroup with a tyrosine kinase inhibitor (lapatinib or tucatinib) could inhibit HER2 signaling and induce accumulated expression of nonfunctional HER2, resulting in increased sensitivity to the sequential HER2-targeting, Ab-drug conjugate DS-8201. Our findings identify clinically relevant subgroups and provide potential therapeutic strategies for HER2-low TNBC subtypes.
- |||||||||| Aidixi (disitamab vedotin) / Rongchang Pharma, Pfizer
Enrollment closed, Phase classification, Trial completion date, Trial primary completion date, Metastases: A Study of RC48-ADC Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer With or Without Liver Metastases (clinicaltrials.gov) - Nov 27, 2023
P2/3, N=301, Active, not recruiting,
Our findings identify clinically relevant subgroups and provide potential therapeutic strategies for HER2-low TNBC subtypes. Recruiting --> Active, not recruiting | Phase classification: P3 --> P2/3 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2023
- |||||||||| Biomarker, Journal, Tumor microenvironment, PARP Biomarker, IO biomarker: Oxidative stress and autophagy-mediated immune patterns and tumor microenvironment infiltration characterization in gastric cancer. (Pubmed Central) - Nov 22, 2023
The low-OARGscore group was predicted to benefit more from Ribociclib, Alisertib, Niraparib, Epirubicin, Olaparib, and Axitinib, while patients in the high-OARGscore group were predicted to benefit more from Afatinib, Oxaliplatin, Paclitaxel, 5-Fluorouracil, Dabrafenib and Lapatinib. Our findings offer a specific method for predicting a patient's prognosis and susceptibility to immunotherapy, as well as a promising insight of oxidative stress and autophagy in GC.
- |||||||||| lapatinib / Generic mfg.
Journal: New Thiazolyl-Pyrazoline Derivatives as Potential Dual EGFR/HER2 Inhibitors: Design, Synthesis, Anticancer Activity Evaluation and In Silico Study. (Pubmed Central) - Nov 18, 2023
The FRPS acts as a risk factor for the prognosis of HCC patients and it can predict the immunotherapy benefits of HCC patients. Among the new synthesized thiazolyl-pyrazolines, compounds 6a, 6b, 10a, and 10b displayed potent anticancer activity toward MCF-7 with IC = 4.08, 5.64, 3.37, and 3.54
- |||||||||| Review, Journal, Metastases: Anti-HER2 Drugs for the Treatment of Advanced HER2 Positive Breast Cancer. (Pubmed Central) - Nov 14, 2023
This article presents new treatment options, discussing the most important findings from clinical trials and real-world reports, clinical benefits and risks of treatment, as well as efficacy of re-treatment with trastuzumab in metastatic breast cancer. New data challenge the current standards, and a number of questions arise regarding the optimal sequence of anti-HER2 targeted therapies, the optimal combination, including endocrine agents in luminal HER2 positive tumors and treatment of special patient population such as patients with brain metastases (BM).
- |||||||||| Five years and counting: A case of a 47-year-old female with De Novo Metastatic HER2 positive disease on multiple lines of treatment (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_1280;
Disease then progressed to the contralateral breast, given 6 cycles of Ado Trastuzumab Emtansine with partial response followed by modified radical mastectomy of the right and toilet total mastectomy of the left breast...Patient was then given 5 cycles of Trastuzumab with Eribulin...The patient will continue to receive Fam-Trastuzumab Deruxtecan-nxki until disease progression and/or unacceptable toxicity...Ongoing research continues to explore new therapeutic approaches and strategies to further improve outcomes for individuals with metastatic HER2-positive breast cancer. This is truly an exciting time for cancer research because what used to be a very deadly disease is now becoming something that we are able manage.
- |||||||||| Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
SOLTI-1718 NEREA Trial: Neratinib in hormone receptor (HR)-positive/HER2-negative HER2-enriched (HER2-E) advanced breast cancer (BC) (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_1101;
P2
According to an exploratory analysis of EGF30008 trial, HER2-E advanced BC patients, despite presenting poor outcomes across treatments, showed benefit from anti-HER2 therapy with lapatinib...Neratinib was combined with exemestane (41.7%), fulvestrant (33.8%) and tamoxifen (25%)...At the time of study close, the hypothesis that neratinib has efficacy in HR+/HER2-, PAM50 HER2-E tumors was not confirmed. We thank PUMA BIOTECHNOLOGY, INC for their provision of Neratinib and financial contribution to the study.
- |||||||||| hydroxychloroquine / Generic mfg., lapatinib / Generic mfg., tamoxifen / Generic mfg.
SMAD4 depletion contributes to endocrine therapy resistance by ERBB signaling in HR+HER2- breast cancer (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_991;
The aberrant activation of autophagy in phenotype rescue experiments was found to reduce the rescue effect of the combination of 4-hydroxytamoxifen (OHT) and lapatinib (LAPA). Taken together, our findings demonstrate that SMAD4 plays a crucial role in endocrine therapy resistance and suggest a reasonable treatment strategy for ER-positive breast cancer patients who are resistant to endocrine therapy.
- |||||||||| Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca
Blocking soluble TNF to Improve potency of trastuzumab deruxtecan by increasing internalization and antitumor innate immune response in a resistant HER2-positive breast cancer model (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_939;
In preclinical models of de novo trastuzumab-resistant tumors, combination of a sTNF blocking agent INB03, (DN), with T-DXd decreases tumor growth compared to T-DXd alone...Methods Nude mice bearing HER2+MUC4+ JIMT-1 tumor, primary resistant to trastuzumab, pertuzumab and lapatinib, were treated with IgG 5 mg/kg, T-DXd 5 mg/kg (T-DXd 5), 2.5 mg/kg (T-DXd 2.5) or 1.25 mg/kg (T-DXd 1.25), DN 10 mg/kg or the combined therapies...Combination of DN with T-DXd in MUC4 expressing HER2+ BC improves response to T-DXd alone by increasing T-DXd internalization and improving anti-tumor innate immune responses in the TME without increasing toxicity. The results suggest this combination should be investigated in clinical trials in patients who have MUC4 expressing tumors when T-DXd is started or become resistant to T-DXd therapy.
- |||||||||| Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
A rare unilateral expression of hand-foot syndrome: a case report (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_658;
Preexisting hemiparesis may play a role in protecting against HFS development, suggesting the involvement of mechanical stress. Patients should be advised to avoid activities that subject the palms and soles to excessive friction.
- |||||||||| Tukysa (tucatinib) / Seagen, Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
Clinical risk factors of Central Nervous System (CNS)-related death in patients with HER2-positive metastatic breast cancer (Hemisfair Ballroom 1-2) - Nov 4, 2023 - Abstract #SABCS2023SABCS_366;
We hypothesize that the association between radiotherapy and CNS-related death may reflect upfront response to systemic cancer-directed treatments of those in patients with DM only or limited CNS disease extension. CNS-only relapse at metastatic presentation portended improved survival than intra- plus extracranial progression, supporting an approach of aggressive local therapy for selected patients.
- |||||||||| Kadcyla (ado-trastuzumab emtansine) / Roche, Perjeta (pertuzumab) / Roche
Journal: Treatments During Pregnancy Targeting ERBB2 and Outcomes of Pregnant Individuals and Newborns. (Pubmed Central) - Oct 30, 2023
Toxic effects were also significantly overreported for trastuzumab-emtansine (cardiovascular malformation: ROR, 4.46 [95% CI, 1.02-19.52]) and lapatinib (intrauterine growth restriction: ROR, 7.68 [95% CI, 3.01-19.59]). In this case-control study of 328 individuals exposed to anti-ERBB2 agents during pregnancy, exposure was associated with a severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments.
- |||||||||| lapatinib / Generic mfg.
Trial completion date, Surgery: Lapatinib Ditosylate Before Surgery in Treating Patients With Recurrent High-Grade Glioma (clinicaltrials.gov) - Oct 30, 2023
P1, N=29, Active, not recruiting,
In this case-control study of 328 individuals exposed to anti-ERBB2 agents during pregnancy, exposure was associated with a severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments. Trial completion date: Oct 2023 --> Oct 2024
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