- |||||||||| Herceptin (trastuzumab) / Roche
Journal: Phenotypic changes of HER2-positive breast cancer during and after dual HER2 blockade. (Pubmed Central) - May 6, 2020 Finally, discontinuation of HER2-targeted therapy in vitro, or acquired resistance to anti-HER2 therapy, leads to restoration of the original HER2-E phenotype. Our findings support the use of maintenance anti-HER2 therapy and the therapeutic exploitation of subtype switching with CDK4/6 inhibition.
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO Biomarker: The trastuzumab era: current and upcoming targeted HER2+ breast cancer therapies. (Pubmed Central) - May 6, 2020
P2 Currently, the combination of trastuzumab, pertuzumab, and taxane chemotherapy are first-line for HER2+/HR- metastatic breast cancer with potential breakthrough therapies such as trastuzumab-deruxtecan (DS-8201a), margetuximab and tucatinib (ONT-380) on the horizon...Each HER2-targeted therapy is then presented by indication, mechanism of action, and relevant clinical trials with subsequent elaboration and contextualization within clinical settings with an epilogue of potential future biomarkers for clinical use in HER2+ BC. We summarize the most significant and updated research in clinical practice relevant to HER2+ BC management and highlight the clinical status of upcoming anti-HER2 agents as well as immunotherapy drugs in combination with anti-HER2 agents.
- |||||||||| pyrotinib (SHR-1258) / Jiangsu Hengrui Medicine, Herceptin (trastuzumab) / Roche
[VIRTUAL] Studies on the efficacy of pyrotinib in the treatment of HER-2 positive advanced solid tumors. () - Apr 29, 2020 - Abstract #ASCO2020ASCO_3787; 11 cases of trastuzumab were changed to anti-HER-2 after treatment failure, of which 2 cases were treated with pirotinib after trastuzumab and lapatinib failed treatment...The common symptoms were diarrhea (100%), hand and foot skin reaction (38%), rash (8%), etc. Grade 3 to 4 adverse events occurred in 1 patient (8%) received pyrotinib plus capecitabine...The treatment of HER-2 positive advanced solid tumors with pyrotinib have good exact affect, and the toxicity could be controlled. Research Funding: None
- |||||||||| Review, Journal: Mechanisms and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs: Insights from in vitro, in vivo, and clinical studies in breast cancer patients. (Pubmed Central) - Apr 28, 2020
In addition, the use of preventive interventions against trastuzumab-induced cardiac dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, remain controversial. Thus, this review aims to summarize and discuss the evidence currently available from in vitro, in vivo, and clinical studies regarding the mechanism and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs.
- |||||||||| lapatinib / Generic mfg., capecitabine / Generic mfg.
Trial completion date, Metastases: Lapatinib +Capecitabine Treatment for Advanced Metastatic Breast Cancer in Women From China (clinicaltrials.gov) - Apr 27, 2020 P3, N=52, Active, not recruiting, Thus, this review aims to summarize and discuss the evidence currently available from in vitro, in vivo, and clinical studies regarding the mechanism and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs. Trial completion date: Dec 2021 --> Apr 2020
- |||||||||| Review, Journal: HER2-targeted therapies - a role beyond breast cancer. (Pubmed Central) - Apr 23, 2020
The experience with gastric cancer suggests that the successes observed in HER2-positive breast cancer might not be replicated in these other tumour types, owing to differences in the level of HER2 overexpression and other aspects of disease biology. In this Review, we describe the current role of HER2-targeted therapies beyond breast cancer and also highlight the potential of novel HER2-targeted agents that are currently in clinical development.
- |||||||||| Tykerb (lapatinib) / Novartis
[VIRTUAL] Combination of bazedoxifene and lapatinib profoundly inhibits estrogen receptor positive (ER+) and Negative (ER-) mammary tumorigenesis (Virtual Meeting: All Session Times Are U.S. EDT) - Apr 13, 2020 - Abstract #AACRI2020AACR-I_65; In a 2-week biomarker study, female MMTV/Neu mice treated with the combinations had significantly decreased proliferation rate (Ki67) in mammary epithelial cells by 74% (p<0.05). These findings indicate that the combination of low-dose daily Baz and weekly Lap is highly effective in preventing ER+ and ER- mammary cancers, and that treatment with the EGFR/HER2 inhibitor Lap once a week is similarly efficacious to daily treatment with divided doses in its cancer inhibitory activity without overt toxicity.
- |||||||||| Tykerb (lapatinib) / Novartis, paclitaxel / Generic mfg.
Journal: Individual or combination treatments with lapatinib and paclitaxel cause potential bone loss and bone marrow adiposity in rats. (Pubmed Central) - Apr 10, 2020 Furthermore, all treatment groups showed increased numbers of bone-resorbing osteoclasts on trabecular bone surfaces, although only the lapatinib group displayed increased levels of osteoclastogenic signal (receptor activator of nuclear factor κΒ ligand/osteoclastogenesis inhibitor osteoprotegrin expression ratio) in the bones. Thus, inhibiting ErbB1 and ErbB2 by lapatinib or blocking cell division by paclitaxel or their combination causes significant trabecular bone loss and bone marrow adiposity involving a switch in osteogenesis/adipogenesis potential, altered expression of some major molecules of the Wnt/β-catenin signalling pathway, and increased recruitment of bone-resorbing osteoclasts.
- |||||||||| Tykerb (lapatinib) / Novartis, paclitaxel / Generic mfg.
Journal: Rapid Self-Assembly of Polymer Nanoparticles for Synergistic Codelivery of Paclitaxel and Lapatinib via Flash NanoPrecipitation. (Pubmed Central) - Apr 6, 2020 Encapsulating either PTX or LAP into nanoparticles increases drug potency (as indicated by the decrease in IC-50 concentration); we observe a 1500-fold increase in PTX potency and a six-fold increase in LAP potency. When PTX and LAP are co-loaded in the same nanoparticle, they have a synergistic effect that is greater than treating with two single-drug-loaded nanoparticles as the combination index is 0.23 compared to 0.40, respectively.
- |||||||||| Tykerb (lapatinib) / Novartis, capecitabine / Generic mfg.
Clinical, Journal, Adverse events: Early Adverse Events predict Survival Outcomes in HER2-positive Advanced Breast Cancer Patients treated with Lapatinib plus Capecitabine. (Pubmed Central) - Apr 2, 2020 Rash and hand-foot syndrome occurring early after the initiation of on lapatinib plus capecitabine were significantly associated with improved OS, while early nausea and vomiting was associated with worse OS. In HER2-positive ABC patients initiating lapatinib plus capecitabine, consideration should be given to more closely monitoring patients at risk of nausea and vomiting, while rash and hand foot syndrome are AE associated with improved survival.
- |||||||||| Tykerb (lapatinib) / Novartis
Journal: Lapatinib sensitivity in nasopharyngeal carcinoma is modulated by SIRT2-mediated FOXO3 deacetylation. (Pubmed Central) - Mar 29, 2020 Collectively, our results suggest the involvement of SIRT2-mediated FOXO3 deacetylation in Lapatinib response and sensitivity, and that SIRT2 can specifically antagonise the cytotoxicity of Lapatinib through mediating FOXO3 deacetylation in both sensitive and resistant NPC cells. The present findings also propose that SIRT2 can be an important biomarker for metastatic and Lapatinib resistant NPC and that targeting the SIRT2-FOXO3 axis may provide novel strategies for treating NPC and for overcoming chemoresistance.
- |||||||||| Avastin (bevacizumab) / Roche, paclitaxel / Generic mfg.
Journal: Establishment of patient-derived tumor xenograft models of mucinous ovarian cancer. (Pubmed Central) - Mar 21, 2020 The pharmacological characterization was undertaken testing the in vivo antitumor activity of both cytotoxic agents (cisplatin, paclitaxel, yondelis, oxaliplatin and 5-fluorouracile) and targeted agents (bevacizumab and lapatinib). These newly established mucinous PDXs do recapitulate mEOC and will be of value in the preclinical development of possible new therapeutic strategies for this tumor type.
- |||||||||| Tykerb (lapatinib) / Novartis, Herceptin (trastuzumab) / Roche, vinorelbine tartrate / Generic mfg.
Retrospective data, Journal, Real-World Evidence: Real-World Data of Triplet Combination of Trastuzumab, Lapatinib, and Chemotherapy in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study. (Pubmed Central) - Mar 21, 2020 P=N/A TLC demonstrated promising effects and tolerable safety in HER2+MBC, even in patients with BM, providing a theoretical basis for clinical practice. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT04001634.
- |||||||||| Journal: Comparison of autophagy inducibility in various tyrosine kinase inhibitors and their enhanced cytotoxicity via inhibition of autophagy in cancer cells in combined treatment with azithromycin. (Pubmed Central) - Mar 21, 2020
We previously reported that gefitinib (GEF) and imatinib (IMA) induce autophagy in epidermal growth factor receptor (EGFR) knock-out A549 and non-BCR-ABL-expressing leukemia cell lines, respectively...We established stable clones expressing the GFP-LC3-mCherry-LC3ΔG plasmid in A549, PC-9, and CAL 27 cell lines and assessed autophagy inducibility by monitoring the fluorescent ratios of GFP-LC3 to mCherry-LC3ΔG using an IncuCyte live cell imaging system during exposure to TKIs viz; GEF, osimertinib (OSI), lapatinib (LAP), lenvatinib (LEN), sorafenib (SOR), IMA, dasatinib (DAS), and tivantinib (TIV)...However, once induced, they appeared to have cytoprotective functions. Thus, blocking TKI-induced autophagy with AZM may improve the therapeutic effect of TKIs in cancer cells.
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