Radboud Applied Pharmacometrics’ Post

Interesting and crucial to have more follow up... novel therapies are promising but we should be careful 

Destiny-Breast06, presented at ASCO, looked at using fam-trastuzumab deruxtecan in HR positive, HER2 ultralow metastatic breast cancer after progression on at least one endocrine therapy.  Patients had to be chemotherapy naive in the metastatic breast cancer setting, and were randomized to either fam-trastuzumab deruxtecan or physician's choice.  Given that patients could have received chemotherapy in the non-metastatic setting, about half of patients had prior exposure anthracyclines, and about 40% of patients had prior exposure to taxanes.  This may explain why physician's choice was capecitabine (59.8%), nab-paclitaxel (24.4%) or paclitaxel (15.8%), although I do wonder if more patients could have been given an anthracycline, as it has demonstrated good efficacy in several clinical trials (https://lnkd.in/ehyU3pWr).   Fam-trastuzumab deruxtecan showed a significant PFS benefit of 13.2 vs 8.1 months (HR 0.62 [0.51-0.74]), while OS was immature (HR 0.83 [0.66-1.05]).  One problem with many of these later line metastatic trials is physician's choice can vary wildly.  For example, in TROPiCS-02, sacituzuamb govitecan was compared against physician's choice in unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer.  There, the top three therapies physicians chose were eribulin, vinorelbine, and gemcitabine.  Again, these are good trials, because they demonstrate that these agents do have clinical benefit in these patient populations, and in the metastatic setting we often end up throwing the kitchen sink at some patients.  But we will need further trials to determine fam-trastuzumab deruxtecan's specific place in therapy in HER2 ultralow patients. #enhertu #breastcancer #trodelvy https://lnkd.in/ewSjKuvm

👉 Follicular lymphoma (FL) represents about 22% of all lymphomas, with a slowly progressive but incurable disease course. Standard treatment involves Rituxan + chemo with high response rates, followed by Rituxan maintenance. Despite this, relapse is common. Small lymphocytic lymphoma (SLL) and CLL are now considered the same disease due to similar therapy responses. 👉 SLL occurs when the disease is limited to lymph nodes, while CLL includes bone marrow and plasma involvement. EOS Intelligence projects follicular lymphoma as a larger market #opportunity than untreated CLL. Roche's Gazyva sales have thrived with expanded iNHL use, but replacing Rituxan poses challenges due to its efficacy and cost-effectiveness. The introduction of Rituxan biosimilars further intensifies this competition. #Therapeutics #Healthcare #MedicalAdvancements #bloodcancer #cancertreatment #competitiveintelligence #marketintelligence #perspectives #eosintelligence #leadership #lifesciences #pharmaceuticals #management #consulting #marketing #marketresearch #oncologydrugs #oncology #biotech --------------------------------------------------------------------------------- Write to me at bhabesh.panigrahi@eos-intelligence to schedule a no-obligation consultation for a winning "Oncology Treatment Strategy"

The first and only #therapy for metabolic-dysfunction associated #steatohepatitis got FDA approval today! Madrigal Pharmaceuticals' Resmetirom, to be marketed as Rezdiffra, is a thyroid hormone receptor beta (THR-β) agonist and will be a game changer in treating #liver disease - reversing #steatosis and #fibrosis would not only positively impact metabolic dysfunction, but also prevent hepatocellular #cancer seeing that #MASH accounts for at least 18% of #HCC cases in the United States alone. #nash #nafld #drugdiscovery #fdaapproval #metabolicdisorders

When real-life adds to clinical data :20,409 reports involving tirzepatide related to 1432 adverse events, the researchers analyzed 7460 reports referring to 286 selected adverse events. Tirzepatide displays an unprecedented glucose- and weight-lowering efficacy, it comes with a similar or even improved safety profile vs GLP-1 receptor agonists.Caveats: FAERS database is based on the spontaneous reporting of adverse events, meaning that "underreporting of some adverse events, especially those occurring several years following drug initiation (ie, thyroid cancer) could occur, [and] public awareness of the association between a drug and a given adverse event might affect reporting frequency," https://lnkd.in/eD6N4R4c

#OnlineFirst w/ #PMT #JPharmTechnol this week, 2 case reports on #drugsafety questions: DeBono & colleagues report on #adverseeffects of nivolumab in RCC in Malta, and Casella & Galli explore appendicitis in patients taking GLP-1 RAs  https://lnkd.in/e3SaEz92 and https://lnkd.in/e4_Uvyjw (respectively) #pharmacists #pharmacy #medicationsafety #medicationmanagement #kidneyhealth #oncology #renalcare #diabetes #diabetesmanagement

Tailoring CLL Treatment: Managing Toxicities and Comorbidities in Targeted Therapies: Alessandra Ferrajoli, MD, discusses the importance of renal function for BCL2 inhibitors to avoid tumor lysis syndrome and cardiovascular history for BTK inhibitors to mitigate arrhythmia risks. #finance #pharmacy #lifesciences

📢 FDA grants accelerated approval to zanubrutinib for r/r follicular lymphoma (BeiGene) ➤ ORR was 69% in the ZO arm and 46% in the obinutuzumab arm (two-sided p-value, 0.0012) ➤ Median DOR was not reached in the ZO arm (95% CI: 25.3 months, NE) and was 14.0 months (95% CI: 9.2, 25.1) for obinutuzumab monotherapy ➤ Estimated DOR rate at 18 months was 69% (95% CI: 58, 78) in the ZO arm #oncology #biotech #biotechnology #regulatoryaffairs #pharma #drugdevelopment #oncologytrials #oncologyresearch #cancer #oncology #regulatoryintelligence #regulatoryprecedent #lymphoma https://lnkd.in/ejXwuUtJ

Oncology Drug Review #8 🌟 Reviewing inotuzumab ozogamicin, an Anti-CD22; Antineoplastic Agent, Antibody Drug Conjugate used for treating relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia in adult and pediatric patients ≥1 year old. Key Points: - Administer IV over 1 hour at a rate of 50 mL/hour. - Allow refrigerated drug to reach room temperature for ~1 hour before infusion. - Use syringe pump and specialized tubing for syringe infusions. - No need for inline filter during administration. - Flush infusion set with NS post-infusion. - Complete dose within ≤8 hours post-reconstitution. - Premedication with corticosteroid, antipyretic, and antihistamine is advised. - Administer prophylactic anti-infectives and conduct surveillance testing during and after treatment. Clinical Considerations: - Cytoreduction before the first dose is recommended. - Maintain a minimum 6-day interval between doses. - Monitor for complete remission and CR with incomplete hematologic recovery. Stay informed for optimal patient care and treatment outcomes! 💼🔬 #Oncology #Pharmacy #MedicalReview

The Hematology Round Up from #ASCO24 (Multiple Myeloma) Phase 3 study results of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) versus VRd for transplant-ineligible patients with newly diagnosed multiple myeloma (IMROZ). https://lnkd.in/d2dRh6Hp Phase 3 randomized study of isatuximab (Isa) plus lenalidomide and dexamethasone (Rd) with bortezomib versus isard in patients with newly diagnosed transplant ineligible multiple myeloma (NDMM TI). https://lnkd.in/dSjVvk7X Daratumumab (DARA) + bortezomib/lenalidomide/dexamethasone (VRd) in transplant-eligible (TE) patients (pts) with newly diagnosed multiple myeloma (NDMM): Analysis of minimal residual disease (MRD) in the PERSEUS trial. Thank you for your attention and enjoy ASCO Disclosure: This Hematology Round Up was supported by Sanofi https://lnkd.in/d9ic5mpy