- |||||||||| simvastatin / Generic mfg., Herceptin (trastuzumab) / Roche
Journal: Targeting the mevalonate pathway to overcome acquired anti-HER2 treatment resistance in breast cancer. (Pubmed Central) - Jul 31, 2020 Implications: The MVA was found to constitute an escape mechanism of survival and growth in HER2+ breast cancer models resistant to anti-HER2 therapies. MVA inhibitors such as simvastatin and zoledronic acid are potential therapeutic agents to re-sensitize the tumors that depend on the MVA to progress on anti-HER2 therapies.
- |||||||||| Tykerb (lapatinib) / Novartis, capecitabine / Generic mfg.
Journal: Improvement in adherence to Capecitabine and Lapatinib by way of a therapeutic education program. (Pubmed Central) - Jul 29, 2020 MVA inhibitors such as simvastatin and zoledronic acid are potential therapeutic agents to re-sensitize the tumors that depend on the MVA to progress on anti-HER2 therapies. This study showed an improvement in adherence to Capecitabine ± Lapatinib among non-adherent patients by way of a therapeutic education program.
- |||||||||| Xeljanz (tofacitinib) / Pfizer, Marche Polytechnic University
Journal: Interaction of the small-molecule kinase inhibitors tofacitinib and lapatinib with membranes. (Pubmed Central) - Jul 28, 2020 While for tofacitinib, no influence to the membrane structure was found, lapatinib causes a membrane disturbance, as concluded from an increased permeability of the membrane for polar molecules. These data may contribute to a better understanding of the cellular uptake mechanism(s) and the side effects of the drugs.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Herceptin (trastuzumab) / Roche, everolimus / Generic mfg.
Journal, PD(L)-1 Biomarker: Applied precision medicine in metastatic pancreatic ductal adenocarcinoma. (Pubmed Central) - Jul 24, 2020 One patient was treated with nintedanib and achieved stable disease for 6 months. Based on our observations, precision medicine approaches are feasible and implementable in clinical routine and may provide molecular-based therapy recommendations for mPDAC.
- |||||||||| MK-2206 / Merck (MSD), lapatinib / Generic mfg., Nerlynx (neratinib) / Puma, Knight Therap, Pierre Fabre
[VIRTUAL] A HER3/DUSP6 loop determines sensitivity to HER2-targeted therapies in breast cancer (On-Demand) - Jul 24, 2020 - Abstract #ESMO2020ESMO_1495; In an acquired resistant model with long-term exposure to Lapatinib, DUSP6 was highly expressed in the early stages of drug treatment and combination of Lapatinib or Neratinib with BCI, a DUSP1 & 6 inhibitor, prevented development of resistant clones...While MK2206 increased the expression of HER2 & HER3, BCI alone or in combination with Lapatinib reduced both HER2 and HER3...Jukka Westermarck. Funding: A K. Albin Johansson Cancer Researcher grant from the Finnish Cancer Institute.
- |||||||||| lapatinib / Generic mfg.
Trial completion, Real-world evidence, Real-world, Metastases: Real World Study of Lapatinib Among Metastatic Breast Cancer Patients (clinicaltrials.gov) - Jul 22, 2020 P=N/A, N=242, Completed, Funding: A K. Albin Johansson Cancer Researcher grant from the Finnish Cancer Institute. Active, not recruiting --> Completed
- |||||||||| [VIRTUAL] Real-world outcomes among HER2+ metastatic breast cancer patients with brain metastases (On-Demand) - Jul 21, 2020 - Abstract #ESMO2020ESMO_626;
To account for changes in systemic treatment options, e.g. introduction of trastuzumab emtansine (T-DM1), analysis was conducted in a subgroup of patients diagnosed after January 1, 2016...Trastuzumab + pertuzumab-based therapy was the most common regimen in both 1L and 2L for patients with and without BM...Lapatinib regimens were used more frequently among BM patients, but were used in only 11-15%, depending on line of therapy...Legal entity responsible for the study: Seattle Genetics. Funding: Seattle Genetics.
- |||||||||| Herceptin (trastuzumab) / Roche, paclitaxel / Generic mfg.
[VIRTUAL] Long-term outcomes of patients with node-negative, ≤3cm, HER2+ breast cancer (BC) enrolled in ALTTO (On-Demand) - Jul 21, 2020 - Abstract #ESMO2020ESMO_548; P3 ALTTO was a large phase III study evaluating the addition of lapatinib (L) to T for early-stage HER2+ BC pts, and its large dataset provides a unique opportunity to delineate the outcomes of pts with HER2+ BC with pathological tumour size (pT)≤3cm/N0...Funding: GSK/Novartis. Clinical trial identification: NCT00490139 (registration date: 22/06/2007); EudraCT Number: 2006–000562–36 (registration date: 04/05/2007); Sponsor Protocol Number: BIG2–06 /EGF106708/N063D.
- |||||||||| Journal: Inhibition of human UDP-glucuronosyltransferase (UGT) enzymes by kinase inhibitors: Effects of dabrafenib, ibrutinib, nintedanib, trametinb and BIBF 1202. (Pubmed Central) - Jul 16, 2020
We have demonstrated previously that the kinase inhibitors (KIs) lapatinib, pazopanib, regorafenib and sorafenib are potent inhibitors of UGT1A1 and UGTs 1A7-1A10...By contrast, BIBF 1202, the major metabolite of nintedanib, did not appreciably inhibit human UGTs, due to the presence of a terminal electronegative group which appears to disfavor enzyme inhibition. Given the potent inhibition of several UGT enzymes, especially UGT1A1, by KIs, characterisation of the DDI potential of newly developed agents in this class is warranted.
- |||||||||| Herceptin (trastuzumab) / Roche
Trial completion, Trial completion date, Trial primary completion date: A Multi-Center Study of Lapatinib in Patients With Trastuzumab-refractory Metastatic Breast Cancer (clinicaltrials.gov) - Jul 15, 2020 P2, N=159, Completed, Given the potent inhibition of several UGT enzymes, especially UGT1A1, by KIs, characterisation of the DDI potential of newly developed agents in this class is warranted. Recruiting --> Completed | Trial completion date: Dec 2021 --> May 2020 | Trial primary completion date: Apr 2021 --> May 2020
- |||||||||| Herceptin (trastuzumab) / Roche
Review, Journal: Current Treatment Options for Breast Cancer Brain Metastases. (Pubmed Central) - Jul 8, 2020 Therefore, there is a need to individualize systemic therapies in BM. Several organizations including the Food and Drug Administration and the American Society of Clinical Oncology now emphasize the inclusion of BM patients in various phases of clinical drug development.
- |||||||||| Tykerb (lapatinib) / Novartis
Journal: DREAM-in-CDM Approach and Identification of a New Generation of Anti-inflammatory Drugs Targeting mPGES-1. (Pubmed Central) - Jul 7, 2020 By using the DREAM-in-CDM approach, lapatinib has been identified as a promising mPGES-1 inhibitor which may have significant anti-inflammatory effects to relieve various forms of pain and possibly treat various inflammation conditions involved in other inflammation-related diseases such as the lung inflammation caused by the newly identified COVID-19. We anticipate that the DREAM-in-CDM approach will be used to repurpose FDA-approved drugs for various new therapeutic indications associated with new targets.
- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, Herceptin (trastuzumab) / Roche
Trial completion, Trial completion date, Trial primary completion date: Bevacizumab in Multiple Phase I Combinations (clinicaltrials.gov) - Jun 30, 2020 P1, N=343, Completed, Trial completion date: Dec 2020 --> Dec 2021 Active, not recruiting --> Completed | Trial completion date: Oct 2020 --> Apr 2020 | Trial primary completion date: Oct 2020 --> Apr 2020
- |||||||||| Tykerb (lapatinib) / Novartis
Journal: One-Pot, Tandem Wittig Hydrogenation: Formal C(sp)-C(sp) Bond Formation with Extensive Scope. (Pubmed Central) - Jun 28, 2020 Chemoselectivity for olefin reduction is observed, and the methodology is demonstrated in the synthesis of lapatinib analogues and a formal synthesis of (±)-cuspareine. Early insights suggest that the chemoselectivity observed in the reduction step is due to partial poisoning of the catalyst, after step one, thus adding to the power of the one-pot procedure.
- |||||||||| Tykerb (lapatinib) / Novartis
Journal: Lapatinib with chemotherapy for gastroesophageal cancer. (Pubmed Central) - Jun 26, 2020 Early insights suggest that the chemoselectivity observed in the reduction step is due to partial poisoning of the catalyst, after step one, thus adding to the power of the one-pot procedure. No abstract available
- |||||||||| Clinical, P2 data, Journal: Pyrotinib or Lapatinib Combined With Capecitabine in HER2-Positive Metastatic Breast Cancer With Prior Taxanes, Anthracyclines, and/or Trastuzumab: A Randomized, Phase II Study. (Pubmed Central) - Jun 19, 2020
Lapatinib plus vinorelbine treatment was tolerable; however, it failed to demonstrate the clinical benefits over vinorelbine alone in patients with HER2 + MBC after progression on both trastuzumab and lapatinib. In women with HER2-positive metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab, pyrotinib plus capecitabine yielded statistically significant better overall response rate and progression-free survival than lapatinib plus capecitabine in this randomized phase II trial.
- |||||||||| Clinical, Review, Journal, PD(L)-1 Biomarker, IO Biomarker: New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?pi. (Pubmed Central) - Jun 19, 2020
Finally, researchers' interest in tumor microenvironment, particularly tumor-infiltrating lymphocytes, and the major role that signaling pathways, such as the PI3K/AKT/mTOR pathway, play in the development of resistance to anti-HER2 therapies have spurred the development of clinical trials evaluating innovative combinations of anti-HER2 with PD-1/PDL-1, CDK4/6 and PI3K inhibitors. However, several questions remain unresolved, like the optimal management of HER2-positive/HR-positive advanced breast cancer and the identification of predictive biomarkers to better define populations that can benefit most from these new therapies and approaches.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Clinical, Journal: Efficacy of osimertinib against EGFRvIII+ glioblastoma. (Pubmed Central) - Jun 19, 2020 Further, osimertinib inhibited D317's growth in vitro and in both heterotopic and orthotopic xenograft models. Additional preclinical studies are warranted to identify EGFRvIII+ GBM's molecular signature most responsive to osimertinib.
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