Eric Lefkofsky’s Post

#MARIPOSA 🧠CNS Metastases Detection: Serial head imaging in the trial allowed for more frequent detection of CNS metastases and robust assessment of treatment effects, making comparisons with studies not using head imaging irrelevant. 🩸Venous Thromboembolic Events: The amivantamab-lazertinib group had a higher incidence of venous thromboembolic events, mostly within the first four months, likely due to rapid tumor cell death. However, severe events and treatment discontinuation rates were low and similar between both groups. 🔬Blinded EGFR-TKI Evaluation: Blinded evaluation of osimertinib and lazertinib showed similar progression-free survival, confirming the efficacy of both drugs and the value of comparing lazertinib directly with osimertinib. https://lnkd.in/gHjPSgfj

Dreams of a future with early curative treatments drives wave of drug development in pre-surgical and perioperative treatment in many tumor types.

A secondary analysis from MARIPOSA 1. In the MARIPOSA study, 89% of patients with analyzable ctDNA in the amivantamab-lazertinib and osimertinib arms had at least one high-risk feature at baseline. 2. Amivantamab-lazertinib significantly improved PFS compared to osimertinib in patients with TP53 co-mutations (HR 0.65; P = 0.003). 3. Amivantamab showed single-agent activity in patients with liver metastases, likely due to its MET activity associated with increased MET expression in the liver. 4. Patients without ctDNA clearance at C3D1 experienced the shortest PFS among all high-risk subgroups. In the MARIPOSA study, these patients had a median PFS of 9.1 months in the osimertinib arm compared to 16.5 months in the amivantamab-lazertinib arm (HR 0.49; P = 0.015). Ref: https://lnkd.in/ggwkqx-z

Ongoing efforts to expand the armamentarium of cell surface targets (DLL3 in this case, for high grade neuroendocrine neoplams) which can be imaged by radionuclide-based tracers. These types of tracers may expand and refine the choice of candidate patients eligible for targeted therapies (e.g., ADCs, radioligand therapy) while moving beyond our reliance on tissue IHC which can be limited by sample availability and heterogeneity

Targeted chemo delivery keeps reshaping practice across tumor types. nejm.org/doi/full/10.10…

The mechanisms underlying #enhanced #immunotherapy efficacy through #exercise. (A) The #antitumor effects of exercise depend on IL-15 signaling pathway, thus enhancing the sensitivity of pancreatic tumor cells to immunotherapy. (B) Exercise increases the infiltration of CD8+ T cells through the CXCL9 or CXCL11/CXCR3 signaling pathway. (C) Exercise influences multiple transcriptional pathways, including promotion of vascular branching and normal vasoconstriction, which improves hypoxia in TME and enhances the efficiency of drug transport.

I'm happy to share my latest research abstract published in the American Gastroenterological Association (AGA) journal: "Radiofrequency Ablation in Combination with an Anti-PDL1 Checkpoint Inhibitor Reduces Tumor Growth and Enhances Anti-Tumor Immunity in a Syngeneic Model of PDAC" The abstract presents preliminary findings on a novel combination therapy for pancreatic ductal adenocarcinoma (PDAC). We investigated how radiofrequency ablation (RFA) combined with anti-PDL1 checkpoint inhibitors affects tumor growth and anti-tumor immune responses. These initial results suggest new possibilities for potentially more effective treatments in pancreatic cancer, combining local tumor destruction with immune system activation. I'm grateful to my co-authors: Lincoln Strickland, Nicolette R. Mardik, Curtis J. Wray, Nirav Thosani, and Jennifer M. Bailey-Lundberg. #CancerResearch #Gastroenterology #Immunotherapy #PDAC #AGAJournal

Important article discussing Second Primary Malignancies After Commercial CAR T Cell Therapy: Analysis of FDA Adverse Events Reporting System (FAERS). In conclusion, SPMs after CAR T represented a small fraction of the AE reports in FAERS. The disproportionality analysis suggests an increased risk of reporting certain SPMs, notably myeloid and T-cell malignancies. The low numbers do not provide conclusive evidence of the risk of SPMs after CAR T therapy. Dedicated registries to study SPMs post CAR T can offer valuable insights for patient care and future development. This becomes pertinent as CAR T therapies expand to nonmalignant conditions 24. Finally, the primary cause of mortality in relapses or refractory hematologic malignancies remains the primary disease. https://lnkd.in/eY74W78P

Peptide receptor radionuclide therapy (PRRNT) is a molecularly targeted radiation therapy involving the systemic administration of a radiolabelled peptide designed to target with receptors overexpressed on tumours. We can use both 90Y-peptide or 177Lu peptides PRRNT is indicated for the treatment of patients with positive expression of sstr2, or metastatic or inoperable NET Eligibility criteria for PRRT : tumor uptake on the Octreoscan being at least as high as the normal liver uptake seen on the planar images Inoperable disease Life expectancy of at least 3–6 months

T cells unhappy with tumoral PGE2. Read our double feature here 👉 https://bit.ly/4dtj9Et