- |||||||||| Herceptin (trastuzumab) / Roche
[VIRTUAL] Prognostic role of distant disease-free interval from completion of adjuvant trastuzumab in HER2-positive early breast cancer: analysis from the ALTTO (BIG 2-06) trial (Channel 3) - Oct 2, 2020 - Abstract #SABCS2020SABCS_1181; In ALTTO, HER2-positive early breast cancer patients were randomized to 1 year of either T alone, lapatinib (L) alone, their sequence (T--> L) or their combination (T+L)...Choice of first-line anti-HER2 therapy was different between the two groups (p=0.022): the majority of patients received T in both groups (61% vs. 65% in groups A and B, respectively), while more patients in group A received L (25% vs. 11%) and less received pertuzumab (8% vs. 17%)... In the ALTTO trial, HER2-positive early breast cancer patients who experienced shorter TFI (i.e. 12 months) following adjuvant T-based therapy had inferior OS after the diagnosis of distant recurrence.
- |||||||||| Tukysa (tucatinib) / Seagen, Herceptin (trastuzumab) / Roche, Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
[VIRTUAL] Comparative analysis of anti-proliferative effects and gene profiling of lapatinib, neratinib, and tucatinib (OnDemand) - Oct 2, 2020 - Abstract #SABCS2020SABCS_688; Neratinib was the most effective HER2-targeted TKI against HER2 -amplified, -mutant, and EGFR -mutant cell lines. This analysis revealed possible mechanisms that may be exploited using combinatorial strategies involving CDK inhibitors, immunotherapies, and targeting DNA repair pathways.
- |||||||||| Tykerb (lapatinib) / Novartis, Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
Journal, Tumor Mutational Burden: Identification of recurrent activating HER2 mutations in primary canine pulmonary adenocarcinoma. (Pubmed Central) - Sep 27, 2020 This study creates a foundation for molecular understanding of and drug development for canine lung cancer. These data also establish molecular contexts for comparative studies in dogs and humans of low mutation burden, never-smoker lung cancer and mutant HER2 function and inhibition.
- |||||||||| Tykerb (lapatinib) / Novartis
Journal: CD36-Mediated Metabolic Rewiring of Breast Cancer Cells Promotes Resistance to HER2-Targeted Therapies. (Pubmed Central) - Sep 25, 2020 Through cDNA microarray analysis, we identify the FA transporter CD36 as a critical gene upregulated in cells with acquired resistance to the HER2 inhibitor lapatinib...In breast cancer patients, CD36 expression increases following anti-HER2 therapy, which correlates with a poor prognosis. Our results define CD36-mediated metabolic rewiring as an essential survival mechanism in HER2-positive breast cancer.
- |||||||||| Tykerb (lapatinib) / Novartis
Journal: Fibroblast-tumor cell signaling limits HER2 kinase therapy response via activation of MTOR and antiapoptotic pathways. (Pubmed Central) - Sep 24, 2020 Here, we show that fibroblasts counteract the cytotoxic effects of HER2 kinase-targeted therapy in a subset of HER2 breast cancer cell lines and allow cancer cells to proliferate in the presence of the HER2 kinase inhibitor lapatinib...These findings indicate that in addition to tumor cell-intrinsic mechanisms that cause constitutive PI3K/AKT/MTOR pathway activation, secreted factors from fibroblasts can maintain this pathway in the context of HER2 inhibition. Our integrated proteomic-phenotypic approach presents a strategy for the discovery of protective mechanisms in fibroblast-rich tumors and the design of rational combination therapies to restore drug sensitivity.
- |||||||||| Jivadco (trastuzumab duocarmazine) / Byondis, Medac
Enrollment closed, Trial completion date, Trial primary completion date, Metastases: TULIP: SYD985 vs. Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov) - Sep 23, 2020 P3, N=436, Active, not recruiting, Our integrated proteomic-phenotypic approach presents a strategy for the discovery of protective mechanisms in fibroblast-rich tumors and the design of rational combination therapies to restore drug sensitivity. Recruiting --> Active, not recruiting | Trial completion date: May 2021 --> May 2022 | Trial primary completion date: Jul 2020 --> Jul 2021
- |||||||||| paclitaxel / Generic mfg.
Clinical, Review, Journal: HER2-targeted treatment for older patients with breast cancer: An expert position paper from the International Society of Geriatric Oncology. (Pubmed Central) - Sep 19, 2020 Although trastuzumab combined with pertuzumab and docetaxel or paclitaxel is recommended first-line in fit patients, taxanes are difficult in vulnerable ones, making a better-tolerated chemotherapy partner highly desirable...Lapatinib activity differs from trastuzumab and causes more side effects and drug interactions that are at higher risk in older patients...Introducing adjuvant therapy lasting less than one year or harnessing neoadjuvant exposure to assess tumour sensitivity and adjust potential rescue treatment accordingly are other key approaches for older patients. These would be particularly helpful for less robust patients or in health systems with limited resources but need further evaluation.
- |||||||||| Tykerb (lapatinib) / Novartis
Journal: Upregulation of pluripotent long noncoding RNA ES3 in HER2-positive breast cancer. (Pubmed Central) - Sep 17, 2020 The results showed that ES3 expression suppressed when HER2 activity was blocked. In summary, for the first time, we found that lncRNA ES3 was significantly upregulated in HER2-positive breast tumors and may contribute to breast cancer proliferation as a downstream target of HER2.
- |||||||||| Herceptin (trastuzumab) / Roche
Review, Journal: Therapeutic Strategies for Human Epidermal Receptor-2 Positive Metastatic Breast Cancer: A Literature Review. (Pubmed Central) - Sep 10, 2020 Tyrosine kinase overexpression can be treated with lapatinib, which has also been approved for improving survival and is used in combination with capecitabine...The addition of new drugs to the chemotherapeutic regimen increases the complexity, burden of side effects, and chances of relapse. Novel anti-HER2 agents have been directed towards therapy making a major paradigm shift.
- |||||||||| Herceptin (trastuzumab) / Roche
Trial primary completion date: Lapatinib in Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer (clinicaltrials.gov) - Sep 9, 2020 P2, N=116, Active, not recruiting, Altogether, combination of carbon-ion beam irradiation and lapatinib has a high potential to kill HER2-positive breast CSCs, causing severe irreparable DNA damage, enhanced autophagy, and apoptosis. Trial primary completion date: Dec 2018 --> Apr 2020
- |||||||||| Review, Journal: Systemic Therapy of Central Nervous System Metastases of Breast Cancer. (Pubmed Central) - Aug 19, 2020
Although much progress remains to be made, a number of effective systemic treatment options are emerging, particularly for patients with HER2-positive disease. Ongoing clinical trials will help define the role of novel agents.
- |||||||||| Kadcyla (ado-trastuzumab emtansine) / Roche
[VIRTUAL] The survival outcomes for the subsequent therapy after treatment with trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer patients (e-poster) - Aug 14, 2020 - Abstract #EBCCI2020EBCC-I_657; Thirteen (43.3%) patients were administered a regimen containing Tmab and/or lapatinib for the first subsequent line after T-DM1...Univariate analysis showed that brain metastases(P<0.004), prior use of Pmab(P=0.03) and the PFS of T-DM1(P=0.03) were significant predictive factors for the PFS of the first subsequent therapy in HER2 positive MBC patients. Conclusions This is the first report to evaluate the survival outcomes for the post-T-DM1 therapy in Japanese HER2-positive MBC patients.Our study showed brain metastases, prior use of Pmab, and PFS of T-DM1 treatment were significantly associated with the PFS of the subsequent treatment after T-DM1 for patients with HER2-positive MBC.
- |||||||||| Kadcyla (ado-trastuzumab emtansine) / Roche
[VIRTUAL] The survival outcomes for the subsequent therapy after treatment with trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer patients (e-poster) - Aug 14, 2020 - Abstract #EBCCI2020EBCC-I_337; Thirteen (43.3%) patients were administered a regimen containing Tmab and/or lapatinib for the first subsequent line after T-DM1...Univariate analysis showed that brain metastases(P<0.004), prior use of Pmab(P=0.03) and the PFS of T-DM1(P=0.03) were significant predictive factors for the PFS of the first subsequent therapy in HER2 positive MBC patients. Conclusions This is the first report to evaluate the survival outcomes for the post-T-DM1 therapy in Japanese HER2-positive MBC patients.Our study showed brain metastases, prior use of Pmab, and PFS of T-DM1 treatment were significantly associated with the PFS of the subsequent treatment after T-DM1 for patients with HER2-positive MBC.
- |||||||||| Tykerb (lapatinib) / Novartis
Clinical, PK/PD data, Journal: Pharmacokinetics of Lapatinib, a Nonrenally Cleared Drug, in Patients With End-Stage Renal Disease on Maintenance Hemodialysis. (Pubmed Central) - Aug 13, 2020 These parameters approximated published values in healthy subjects and demonstrated that renal impairment and hemodialysis did not affect lapatinib pharmacokinetics. The results of the present study in this renally impaired population, the only such information available to date, support the drug's label and are valuable in view of the recognized difficulties in enrolling organ-impaired patients in oncology trials.
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