- |||||||||| Kisqali (ribociclib) / Novartis, ONC201 / Chimerix, Verzenio (abemaciclib) / Eli Lilly
Acquired sensitivity strategies in ER+ breast cancer progressing on CDK4/6 and mTOR inhibitors (Hall 1) - Oct 26, 2021 - Abstract #SABCS2021SABCS_1089; We used isogenic breast cancer cell lineages sensitive and resistant to CDK4/6 inhibitors, ribociclib and abemaciclib, and the mTOR inhibitor, everolimus, to determine the efficacy of drug combinations targeting the acquired resistance JNK, MAPK and AKT pathways...Our results indicate increased potency in the resistant cells to the combination therapies with JNK and TIC10/ONC201 inhibitors which are currently seeing promise in clinical trials...In conclusion, our study leveraged our patient data cohorts as well as pre-clinical models to identify acquired sensitivity to JNK, MAPK and AKT inhibition. With the linking of both patient derived data with isogenic cell line driven experiments, our study provides validated findings in various settings strengthening the potential of clinical applications of these targetable pathways.
- |||||||||| Herceptin (trastuzumab) / Roche
A phase II trial of lapatinib and everolimus for HER2 positive metastatic breast cancer (Hall 1) - Oct 26, 2021 - Abstract #SABCS2021SABCS_800; The combination of lapatinib and everolimus was not found to be an active regimen in patients who had previously progressed on at least one line of prior HER2 targeted therapy. We would not recommend further exploration of this combination in phase II or phase III trials in this patient population.
- |||||||||| Piqray (alpelisib) / Novartis, Ibrance (palbociclib) / Pfizer
Overexpressed cyclin D1 and CDK4 proteins are responsible for the resistance to CDK4/6 inhibitor in breast cancer that can be reversed by PI3K/mTOR inhibitors (Hall 1) - Oct 26, 2021 - Abstract #SABCS2021SABCS_653; The tumors from breast cancer patients who progressed after palbociclib treatment had significantly higher protein expression of Cyclin D1, CDK4, p-AKT and p-4E-BP1 than the paired samples before palbociclib treatment. In conclusion, our findings suggest that overexpressed Cyclin D1 and CDK4 proteins lead to the resistance to CDK4/6 inhibitor and PI3K/mTOR inhibitors are able to restore the sensitivity to CDK4/6 inhibitors, which provides the biomarker and rationale for the combinational use of CDK4/6 inhibitors and PI3K/mTOR inhibitors after CDK4/6 inhibitor resistance in breast cancer.
- |||||||||| LCL161 / Novartis, spartalizumab (PDR001) / Novartis
Trial completion date, Trial primary completion date, Combination therapy: A Study of PDR001 in Combination With LCL161, Everolimus or Panobinostat (clinicaltrials.gov) - Oct 25, 2021 P1, N=298, Active, not recruiting, Therefore, genotype-matched therapies may help patients with refractory gynecological cancers achieve better outcomes. Trial completion date: Aug 2022 --> Feb 2022 | Trial primary completion date: Sep 2021 --> Dec 2021
- |||||||||| xentuzumab (BI-836845) / Boehringer Ingelheim
Trial completion date, Trial primary completion date, Combination therapy, Metastases: The XENERA (clinicaltrials.gov) - Oct 25, 2021 P2, N=103, Active, not recruiting, Trial completion date: Oct 2022 --> Oct 2023 | Trial primary completion date: Oct 2021 --> Oct 2023 Trial completion date: Nov 2022 --> Mar 2022 | Trial primary completion date: Dec 2021 --> Aug 2021
- |||||||||| everolimus / Generic mfg.
Preclinical, Journal: The rapamycin analog Everolimus reversibly impairs male germ cell differentiation and fertility in the mouse1. (Pubmed Central) - Oct 22, 2021 Return to control values following a recovery period was variable for each of the measured parameters and was duration- and dose-dependent. Together, these data indicate rapalogs exerted a dose-dependent restriction on overall growth of juvenile and adult mice and negative impact upon spermatogenesis that were largely reversed; following treatment cessation, males from all treatment groups were able to sire offspring.
- |||||||||| Avastin (bevacizumab) / Roche
Review, Journal, IO biomarker: A narrative review of targeted therapies in meningioma. (Pubmed Central) - Oct 22, 2021 Clinical trial results from sunitinib [multitargeted tyrosine kinase inhibitor (TKI)], bevacizumab (VEGF inhibitor), everolimus (mTOR inhibitor) and bevacizumab revealed some promising tumor response in recurrent meningiomas. Currently, many clinical trials including targeted therapies, antiangiogenic agents and immunotherapies are being investigated or under consideration.
- |||||||||| cyclosporin A microemulsion / Generic mfg., everolimus / Generic mfg.
Review, Journal: The Effect of Immunosuppressive Drugs on MMPs Activity in The Walls of Blood Vessels - A Systematic Review. (Pubmed Central) - Oct 22, 2021 The deceases of the patients with the functioning graft who were diagnosed with the cardiovascular system diseases, constitute 50% of all renal transplant recipients. Immunosuppressive treatment leads to many pathological alterations within the organs and tissues and additionally they undoubtedly affect the activity of MMPs in the wall of the vessels.
- |||||||||| everolimus / Generic mfg.
[VIRTUAL] PV+ Interneurons Are Non-Cell Autonomously Dysregulated in Depdc5-Associated Epilepsies () - Oct 21, 2021 - Abstract #ANA2021ANA_224; We further found that perineuronal nets (PNN) and parvalbumin (PV) + interneuron (IN) are impaired non-cell autonomously through microglialmediated neuroinflammation in a response to the downregulated microglial inhibitory molecule, CD200, and the severely disrupted homeostasis in mutant cortical excitatory neurons. Therapeutically, treatment with Everolimus restored both cell-autonomous pyramidal neuron and non-cell autonomous PV+ IN impairments, and rescued severe seizures, suggesting critical roles of PV+ INs in the epileptogenesis of MTOR-related MCD.
- |||||||||| Inlyta (axitinib) / Pfizer, Keytruda (pembrolizumab) / Merck (MSD), Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] Treatment of PLA2R-Negative Membranous Nephropathy in the Setting of Immune Checkpoint Inhibitor and Renal Cell Carcinoma () - Oct 17, 2021 - Abstract #KIDNEYWEEK2021KIDNEY_WEEK_1383; He subsequently progressed after a 14-week course with second-line cabozatinib (TKI) and was initiated on third-line levatinib (TKI) plus everolimus (mTOR inhibitor) two months prior to presenting with severe diarrhea...MN can also present as a paraneoplastic lesion, but it is rarely associated with RCC and the presentation did not correlate with his improved CT scan. Given his deteriorating kidney function, treatment with rituximab was fortunately successful and allowed for continued treatment with durable cancer response.
- |||||||||| Prolia (denosumab) / Amgen, Daiichi Sankyo, Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
[VIRTUAL] Recurrent Renal Cell Carcinoma Post Renal Transplantation () - Oct 17, 2021 - Abstract #KIDNEYWEEK2021KIDNEY_WEEK_1376; Immunosuppression(IS) included Mycophenolate Mofetil (MMF), Tacrolimus (FK), and steroids (S)...1 year later, he developed BK viremia, and IS was changed to Everolimus and S. 2 years post-Tx, RCC metastasis was detected only in the pancreas head and tail...IS involved MMF, Cyclosporine, and S. History was significant for L nephrectomy 3 years pre-Tx for RCC...Treatment involved change in IS to Sirolimus and Azathioprine...His current treatment involves TKI with Denosumab, and he still has a functioning allograft...We suspect that recurrent disease arises from micrometastatic tumor cells that escape immune surveillance. RTR with a history of RCC prior to Tx should be monitored closely for metastatic recurrence post Tx.
- |||||||||| everolimus / Generic mfg., clopidogrel / Generic mfg.
Preclinical, Journal: Microvasculature in murine tracheal allografts after combined therapy with clopidogrel and everolimus. (Pubmed Central) - Oct 16, 2021 Based on this case we recommend that in NET patients with high chromogranin A levels, we check for signs of proximal tubulopathy before starting mtor inhibitor therapy. These data demonstrate that the ability of everolimus to reduce the development of post-transplant obliterative bronchiolitis is not caused by microvascular protection and has no synergistic effects with clopidogrel in acute airway rejection.
- |||||||||| everolimus / Generic mfg.
Retrospective data, Review, Journal: Everolimus in Advanced Breast Cancer: A Systematic Review and Meta-analysis. (Pubmed Central) - Oct 15, 2021 In patients with HER2 (+) disease, the benefit is limited for those with hormone receptor (-) disease. Given the approval and use of newer drugs in MBC, clinical trials and real-world data are needed to confirm the benefit of everolimus and define the best treatment sequence strategy to adopt in that setting.
- |||||||||| everolimus / Generic mfg.
[VIRTUAL] The Effect Of Rhabdomyomas On Underlying Cardiomyopathy: A Case Report (ePosters) - Oct 14, 2021 - Abstract #AHA2021AHA_7138; Due to worsening heart failure, everolimus therapy initiated to target potential rhabdomyomas while awaiting genetic testing for tuberous sclerosis...However, he continues to have ventricular dilation and mild dysfunction attributable to cardiomyopathy. It is unlikely that mother’s SARS-CoV-2 infection played a role as infant tested negative and clinical picture was not consistent with myocarditis.
|