- |||||||||| Jakafi oral (ruxolitinib) / Novartis, Incyte, Afinitor (everolimus) / Novartis
Journal, Heterogeneity, IO Biomarker: Heterogeneity and Plasticity of Human Breast Cancer Cells in Response to Molecularly-Targeted Drugs. (Pubmed Central) - Nov 5, 2019 Silencing the identified alternative proteins via siRNA resulted in significant drop in the LC50 of the selected molecularly-targeted drugs cells resistant to ruxolitinib (via targeting Akt), everolimus (via targeting EGFR, MAPK7, RPS6KA5, and HER2), and erlotinib (via silencing Bcl2 and BIRC8). Our data indicates that targeting well-selected alternative proteins could potentially sensitize the resistant cells to the effect of the molecularly-targeted treatment.
- |||||||||| Afinitor (everolimus) / Novartis
Journal: Tumor hypoxia directed multimodal nanotherapy for overcoming drug resistance in renal cell carcinoma and reprogramming macrophages. (Pubmed Central) - Nov 2, 2019 Copper-free 'click' chemistry was utilized for conjugating SMA-TPGS with Acetazolamide (ATZ, a CA IX-specific targeting ligand)...Near-infrared (NIR) imaging of CA IX-SMA-TPGS-S0456 in Evr-res A498 RCC model exhibited significant accumulation of CA IX-oligomer in tumor core with >3-fold higher tumor uptake as compared to control. In conclusion, this proof-of-concept study demonstrates versatile tumor hypoxia directed nanoplatform that can work in synergy with existing drugs for reversing drug-resistance in RCC accompanied with re-education of tumor-associated macrophages, that could be applied universally for several hypoxic tumors.
- |||||||||| everolimus / Generic mfg.
Clinical, Journal: Stomatitis associated with mammalian target of rapamycin inhibition: A review of pathogenesis, prevention, treatment, and clinical implications for oral practice in metastatic breast cancer. (Pubmed Central) - Oct 31, 2019 In conclusion, this proof-of-concept study demonstrates versatile tumor hypoxia directed nanoplatform that can work in synergy with existing drugs for reversing drug-resistance in RCC accompanied with re-education of tumor-associated macrophages, that could be applied universally for several hypoxic tumors. Oral health care providers are on the frontline of oral health care for patients with metastatic breast cancer and are uniquely positioned to provide patient education, advocate accurate reporting of mIAS, and support early identification, monitoring, and prompt intervention to mitigate the severity and duration of this manageable, potentially dose-limiting AE.
- |||||||||| everolimus / Generic mfg.
Clinical, Journal: Outcomes Among Patients Undergoing Distal Left Main Percutaneous Coronary Intervention. (Pubmed Central) - Oct 31, 2019 P=N/A Oral health care providers are on the frontline of oral health care for patients with metastatic breast cancer and are uniquely positioned to provide patient education, advocate accurate reporting of mIAS, and support early identification, monitoring, and prompt intervention to mitigate the severity and duration of this manageable, potentially dose-limiting AE. Among patients with distal LM bifurcation disease in the EXCEL trial randomized to PCI, 3-year adverse outcomes were worse with planned 2-stent treatment compared with a provisional 1-stent approach, a difference that was confined to patients without major involvement of both LM side branch vessels.
- |||||||||| Afinitor (everolimus) / Novartis
Journal: Risks and benefits of everolimus. (Pubmed Central) - Oct 30, 2019 Among patients with distal LM bifurcation disease in the EXCEL trial randomized to PCI, 3-year adverse outcomes were worse with planned 2-stent treatment compared with a provisional 1-stent approach, a difference that was confined to patients without major involvement of both LM side branch vessels. In the current version of this journal, Ferreira and colleagues (1) report the outcome of a 12-month, prospective, randomized, controlled trial from Sao Paolo, Brazil comparing mycophenolate (MPA) and everolimus in low/standard risk, de-novo kidney transplant recipients from extended criteria deceased donors (donor age >60 years, mean kidney donor profile index 89.
- |||||||||| Afinitor (everolimus) / Novartis
Preclinical, Journal: The Effects of Short-Term Immunosuppressive Therapy on Redox Parameters in the Livers of Pregnant Wistar Rats. (Pubmed Central) - Oct 29, 2019 Among the groups of dams treated with immunosuppressive drugs, the highest significant concentration of GSH was found in the livers of rats treated with cyclosporine A, mycophenolate mofetil and glucocorticosteroid. Immunosuppressive therapy during pregnancy affects the oxidoreductive balance in the livers of rats, depending on the regimen used.
- |||||||||| Afinitor (everolimus) / Novartis
Glioblastoma organoids: a model system for patient-specific therapeutic testing (Ballroom Lawn) - Oct 29, 2019 - Abstract #SNO2019SNO_1341; Two GBOs had downstream NF1 mutations that responded to the MEK inhibitor trametinib...One GBO line was found to have a PI3K mutation and responded dramatically to mTOR inhibition via everolimus...This novel culturing method of GBOs maintains intertumoral and intratumoral heterogeneity and allows for therapeutic testing within two weeks of neurosurgical resection. As clinical sequencing because increasingly prevalent, GBOs may become a valuable tool to functionally test mutation-specific treatment strategies in a patient-specific manner within a clinically relevant time frame.
- |||||||||| Afinitor (everolimus) / Novartis
A phase 0 pharmacodynamic and pharmacokinetic study of everolimus in vestibular schwannoma (VS) and meningioma patients (Grand Canyon 1-6) - Oct 29, 2019 - Abstract #SNO2019SNO_810; In patients with meningioma or VS, treatment with everolimus leads to incomplete inhibition of mTORC1 signaling and upregulation phospho-ERK. These data may explain the limited anti-tumor effect of everolimus observed in clinical studies for NF2 patients and identify upregulation of phospho-ERK as a likely resistance mechanism that could be addressed with combination therapies.
- |||||||||| Avastin (bevacizumab) / Roche, Lutathera (lutetium Lu 177 dotatate) / Novartis, Afinitor (everolimus) / Novartis
Efficacy of 177Lu-Dotatate therapy in recurrent anaplastic meningioma (Ballroom Lawn) - Oct 29, 2019 - Abstract #SNO2019SNO_521; The transient increase in tumor volume after the first dose in this case may have represented delayed treatment effect or pseudoprogression. A phase II clinical trial is currently being activated to determine the progression-free survival associated with 177Lu-Dotatate in patients with recurrent meningioma.
- |||||||||| everolimus / Generic mfg.
Enrollment closed, Trial completion date, Trial primary completion date: Safety and Efficacy of Everolimus Treatment in Liver Transplantation for Liver Cancer (clinicaltrials.gov) - Oct 29, 2019 P4, N=336, Active, not recruiting, However, it failed to meet primary outcome of extending PFS in this population. Recruiting --> Active, not recruiting | Trial completion date: Aug 2019 --> Jan 2021 | Trial primary completion date: Aug 2019 --> Jan 2021
- |||||||||| Opdivo (nivolumab) / BMS
Trial completion date, PD(L)-1 Biomarker, IO biomarker, Metastases: Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025) (clinicaltrials.gov) - Oct 28, 2019 P3, N=1068, Active, not recruiting, Our results imply that only early EVL conversion induces key changes in the post-transplant immune response, preserving an efficient anti-viral response, but simultaneously showing a limited ability to counteract the cytotoxic response to the allograft. Trial completion date: Aug 2019 --> Jun 2020
- |||||||||| Afinitor (everolimus) / Novartis
Review, Journal: Management of Advanced Small Bowel Cancer. (Pubmed Central) - Oct 27, 2019 Immunotherapy for small bowel adenocarcinomas, several multikinase inhibitors in resistant GIST patients, as well as everolimus and Lu-DOTATATE in neuroendocrine tumors are only few of the novel therapeutic options that have changed, or may change in the future, the therapeutic landscape of these rare cancers. Larger and more powerful studies on the molecular profile of these tumors may lead to a better design of clinical trials, which eventually would provide our patients with more efficacious treatments to improve both overall survival and quality of life.
- |||||||||| everolimus / Generic mfg.
Trial completion date, Trial primary completion date: RAD001 for Patients With Radioiodine Refractory Thyroid Cancer (clinicaltrials.gov) - Oct 24, 2019 P2, N=33, Active, not recruiting, Adjunctive everolimus resulted in sustained reductions in seizure frequency after 1 year and was well tolerated in paediatric patients with treatment-refractory seizures associated with tuberous sclerosis complex. Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2019 --> Dec 2020
- |||||||||| Trial withdrawal: Myfortic in High MELD Liver Transplantation (clinicaltrials.gov) - Oct 21, 2019
P=N/A, N=0, Withdrawn, Active, not recruiting --> Completed | Trial completion date: Dec 2020 --> Oct 2019 Completed --> Withdrawn
- |||||||||| Afinitor (everolimus) / Novartis
Future Directions in Endocrine Therapy for Advanced HR+/HER2- Breast Cancer (Hemisfair Ballroom -3rd level) - Oct 19, 2019 - Abstract #SABCS2019SABCS_1989; Substantial advances over the prior decades have demonstrated the efficacy of endocrine monotherapies, including aromatase inhibitors, tamoxifen, and fulvestrant, in controlling disease and prolonging survival...The CDK4/6 inhibitors (CDK4/6i): palbociclib, abemaciclib, and ribociclib, have uniformly demonstrated efficacy in the first-line and pretreated settings in prolonging progression free survival, with hazard ratios across at least 8 randomized trials (PALOMA, MONARCH, MONALEESA series) ranging from 0.50-0.55...Additionally, in the setting of endocrine resistance, a deeper understanding of resistance signaling, such as the mTOR/PI3kinase/AKT pathway, has led to the development and approval of active therapies, including everolimus and alpelisib, with further agents in development...Substantial ongoing work attempts to characterize the heterogenous genomic alternations which underlie resistance to endocrine and targeted therapies, and novel agents matched to these specific mutations are in development. Moving beyond CDK4/6i, we are now entering a new era of personalized and targeted therapy for metastatic HR+ HER-2 negative breast cancer, with the potential to provide significant benefit to the many patients with this disease.
- |||||||||| Afinitor (everolimus) / Novartis, Rituxan (rituximab) / Roche, Biogen
Clinical, Review, Journal: Maintenance Therapy in Diffuse Large B Cell Lymphoma and Mantle Cell Lymphoma. (Pubmed Central) - Oct 18, 2019 In randomized, controlled clinical trials, this approach has successfully prolonged overall survival in some MCL clinical settings, including after autologous stem cell transplantation and after R-CHOP induction, but has generally been unsuccessful in DLBCL...Thus, future strategies to improve DLBCL treatments should focus on improved induction and possibly consolidation regimens rather than maintenance. In MCL, maintenance therapy will continue to play a role in the near future, although in both diseases, applying novel immunotherapies with the potential to eradicate residual disease clones persisting after induction may be the most successful strategy to improve patient outcomes.
- |||||||||| Afinitor (everolimus) / Novartis
Review, Journal: Advanced typical and atypical carcinoid tumours of the lung: management recommendations. (Pubmed Central) - Oct 18, 2019 Various treatment options-including somatostatin analogs, peptide receptor radioligand therapy, and biologic systemic therapy, specifically with the mtor (mechanistic target of rapamycin) inhibitor everolimus-are now available and are presented in a treatment algorithm...Many variables have to be considered in managing these tumours that have received little attention. Education for treating physicians is needed.
- |||||||||| Afinitor (everolimus) / Novartis
Second line treatment in metastatic uterine pecoma () - Oct 16, 2019 - Abstract #ESGO2019ESGO_1200; We report the effect of pazopanib for a patient with metastatic uterine PEComa progressing on everolimus...For the bone metastasis denosumab was initiated...Conclusion Our report provides evidence that anti-angiogenic targeted therapy with pazopanib, a multi TKI, is an effective second line treatment for metastatic malignant PEComas progressing after mTOR inhibition. The toxicity profile of the association was acceptable in line with the previously reported toxicities of the respective drugs.
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