Caprelsa (vandetanib) / Sanofi, Esteve - LARVOL DELTA

Haematological toxicities with targeted drugs in tumors: A systematic review and network meta-analysis of randomized controlled trials (ASH 2025) - "1 patient treated with sorafenib plus chemotherapy was reported to have died as a result of pancytopenia and 1 patient treated with chemotherapy (gemcitabine plus cisplatin) died due to anemia. Our study confirmed that chemotherapy with or without a placebo, one targeted drug with chemotherapy was associated with more severe hematologic toxicities compared with the use of one targeted drug, tepotinib plus gefitinib, tivantinib plus erlotinib. In the targeted drug monotherapy category, for the primary outcome, we found that alectinib and gefitinib had a higher risk of all-grade (grade 1-5) and severe-grade (grade 3-5) anemia, respectively...Ganitumab plus chemotherapy had the highest risk of grade 1-5 anemia and thrombocytopenia. Afatinib plus chemotherapy had the highest risk of grade 3-5 anemia and thrombocytopenia. Ramucirumab plus chemotherapy had the highest risk of grade 1-5 and 3-5 neutropenia. Veliparib plus chemotherapy had the highest risk of grade 1-5 and 3-5..."

Retrospective data • Review • Febrile Neutropenia • Leukopenia • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia

Use of Multilevel Network Meta Regression (ML-NMR) Model in RET Mutation-Positive Medullary Thyroid Cancer (MTC) (ISPOR-EU 2025) - "This case study demonstrates the feasibility of using ML-NMR for comparing time to event outcomes across studies. The findings suggest that selpercatinib is more efficacious than cabozantinib, vandetanib, and placebo for MTC."

Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

Selpercatinib plus cemiplimab in RET positive medullary thyroid cancer patient with skin cancers. (PubMed, Tumori) - "The combination of selpercatinib and cemiplimab was possible, with no new safety signals observed."

Journal • Basal Cell Carcinoma • Genetic Disorders • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

A Patient's Journey Toward a Cure: Drugging the Medullary Thyroid Cancer Surfaceome with T Cell Engagers Targeting CEA, GFRA4 and DLL3 as Monotherapy and In Combination with TKIs (SITC 2025) - "In the setting of progressive metastatic MTC, TKIs (selpercatinib, cabozantinib and vandetanib) can prolong survival for some patients, at the expense of side effects and cumulative toxicities.1–3 In particular, daily selpercatinib administration resulted in a robust overall survival (OS) benefit in MTC patients harboring RET mutations.2 However, no randomized trial has demonstrated any OS benefit in RET wild-type patients...Eric Tran (EACRI) and Jena French (UC-Denver) for many thoughtful discussions over the years. They have both gone out of their way to support and inspire."

Clinical • Combination therapy • Monotherapy • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • DLL3 • IFNG • RET

Vandetanib and Everolimus in Treating Patients With Advanced or Metastatic Cancer (clinicaltrials.gov) - P1 | N=151 | Completed | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Completed | Trial completion date: May 2026 ➔ Oct 2025 | Trial primary completion date: May 2026 ➔ Oct 2025

Trial completion • Trial completion date • Trial primary completion date • Oncology

Targeting metabolic and epigenetic reprogramming in metastatic fumarate hydratase-deficient renal cell carcinoma. (PubMed, Clin Exp Metastasis) - "These include immune checkpoint inhibitors (nivolumab, tislelizumab, sintilimab, avelumab), multi-tyrosine kinase inhibitors (cabozantinib, erlotinib, lenvatinib, axitinib, vandetanib), and PARP inhibitors (talazoparib). The most promising combinations are nivolumab/cabozantinib (N = 5, objective response rate (ORR): 100%), lenvatinib/tislelizumab (N = 14, ORR: 93.3%), bevacizumab/erlotinib (N = 43, ORR: 72%), and sintilimab/axitinib (N = 19, ORR: 63.1%). In this review, we will provide a detailed overview of ongoing clinical trials, highlighting the roles of metabolic and epigenetic reprogramming, as well as pro- oncogenic signaling, which together form the backbone for emerging novel targeted treatment strategies. Targeting these specific signaling pathways will shift the therapeutic landscape toward personalized medicine in metastatic FHdRCC."

Journal • Review • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • FH

Vascular endothelial cells and angiogenesis. (PubMed, Pharmacol Res) - "Ponatinib, regorafenib, and vandetanib are FDA-approved VEGFR, Tie2, and Ephrin receptor blockers used in the treatment of various malignancies. Other disorders characterized by aberrant angiogenesis include diabetic retinopathies and neovascular age-related macular degeneration."

Journal • Review • Age-related Macular Degeneration • Diabetic Retinopathy • Macular Degeneration • Oncology • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • ANGPT1 • EFNA1 • FLT1 • HGF • MET • NRP1 • NRP2

Cutaneous Coccidioidomycosis Mimicking Rosacea in Immunosuppressed Patient, Arizona, USA, 2024. (PubMed, Emerg Infect Dis) - "Lesions resolved with fluconazole treatment, but blue-gray hyperpigmentation persisted, likely linked to vandetanib. This case highlights diagnostic challenges in endemic fungal infections and rare drug-associated hyperpigmentation."

Journal • Dermatitis • Dermatology • Immunology • Infectious Disease • Respiratory Diseases • Rosacea

Design, synthesis, anticancer evaluation, biological screening, and computational study of novel 6,7-dimethoxyquinazoline derivatives as VEGFR-2 inhibitors and apoptotic inducers. (PubMed, Eur J Med Chem) - "Moreover, the MTT viability test for compounds 9a, 9b, and 9c demonstrated less cytotoxicity against normal fibroblast cells (WI38), revealing enhanced safety profiles with IC50 values of 28.04, 219.79, and 43.77 μM, respectively, compared to Sorafenib (IC50 = 26 μM). Enzyme inhibition assays revealed that compounds 9a-c effectively inhibited EGFR and VEGFR-2, confirming the multi-targeting potential of this series of compounds."

Journal • Hematological Malignancies • Leukemia • Oncology • BCL2 • CASP3 • EGFR • KDR

DFT Structural and UV-Vis Spectral Insights into Photosensitivity of Vandetanib: A Dual EGFR/SARS-CoV-2 Mpro Inhibitor. (PubMed, Pharmaceuticals (Basel)) - " This study provides molecular-level insights into the structural and photophysical origins of vandetanib's photosensitivity. The findings improve understanding of its adverse effects and can inform the safer design of EGFR-targeting drugs with reduced phototoxic risks."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • EGFR

FDA Removes Risk Evaluation and Mitigation Strategies (REMS) for Caprelsa (vandetanib) (FDA) - "After over more than a decade of oversight, REMS assessments reported no cases of Torsades de pointes or unexplained sudden deaths among U.S. patients taking Caprelsa. Clinical data also showed no concerning patterns of heart rhythm problems...Caprelsa will remain available with the same prescribing information, but health care providers will no longer need special certification or extra monitoring beyond standard clinical care."

FDA event • Thyroid Gland Carcinoma

Pralsetinib (Phase 1/2 ARROW Trial) Compared With Best Available Therapy (External Control) in Pretreated RET Fusion+ NSCLC (IASLC-WCLC 2025) - P1/2 | "Most frequently received BAT were tyrosine kinase inhibitors (66.7%; 29.6% investigational agents, 25.9% cabozantinib, 7.4% vandetanib, 3.7% alectinib) and chemotherapy (25.9%)...Conclusions : This RW, multi-center study found that 2L+ treatment with pralsetinib in advanced RET fusion-positive NSCLC was associated with higher ORR and significantly improved OS and PFS compared to BAT, even after adjusting for population differences. Limitations of RW data include missing data and potential unmeasured confounding, which this study aimed to mitigate through rigorous analytical methods."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • RET

Evolving Research in the Treatment of Patients With Advanced/Metastatic Thyroid Cancer (Medscape) - "Dr. Brose: The agents that I just mentioned are mostly used in differentiated thyroid cancer. I think the field is now developed enough that people feel medullary is different from anaplastic is different from differentiated thyroid cancer...One drug, vandetanib, has been through phase 2 and phase 3 testing for hereditary medullary thyroid cancer.[5] In patients who have RET mutations, vandetanib has been FDA approved. They are now looking for additional indications for medullary thyroid cancer, and I believe they have a phase 3 study in the pediatric population. So medullary thyroid cancer has a few agents in trials. There is a phase 3, multi-institutional study of a PPAR gamma agonist in anaplastic thyroid cancer."

Interview

Thyroid cancer: From molecular insights to therapy (Review). (PubMed, Oncol Lett) - "Molecularly targeted therapies constitute the cornerstone of current strategies, with vemurafenib inhibiting BRAF/MEK in PTC, sorafenib acting as a multikinase suppressor in FTC, vandetanib blocking RET in MTC and berberine-doxorubicin combinations overcoming chemoresistance in ATC. Metabolic interventions, including metformin for glucose modulation in PTC and novel delivery systems such as micelle-encapsulated AB3 for MTC, demonstrate translational potential. The present review summarizes molecular mechanisms, diagnostic tools and emerging therapies while emphasizing the necessity of subtype-specific approaches to improve clinical outcomes in thyroid oncology."

IO biomarker • Journal • Review • Genetic Disorders • Hematological Disorders • Lung Adenocarcinoma • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Obesity • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF • CREB3L1 • MALAT1 • PD-1 • PD-L1 • RET • STC • STC1 • STMN1 • TERT • TP53

"Transcriptomic Profiling Unveils Novel Therapeutic Options for Drug-Resistant Temporal Lobe Epilepsy". (PubMed, Eur J Pharmacol) - "Based on differential RNA-Seq profiling, we therefore propose erlotinib, danazol, rucaparib, ponatinib, and panobinostat."

Journal • CNS Disorders • Epilepsy

A functional prognostic model predicts progression free survival in patients with relapsed chronic lymphocytic leukemia treated with ibrutinib + venetoclax (IWCLL 2025) - P2 | "Our machine learning model selected only functional features as most predictive of PFS, ex vivo sensitivity to vandetanib (VEGFR/EGFR inhibitor), ruxolitinib (JAK1/2 inhibitor) + venetoclax (Bcl-2i), and acalabrutinib (BTKi) + ZSTK474 (PI3Ki); relative expression/phosphorylation level of Bcl-2|BTK (pY223) and p90RSK (pS380)|PLCγ2 (pY759); and a high proportion of CD8+ T cells. i) Genetic subgroups of CLL show distinct ex vivo drug sensitivities, and protein profiles have the highest predictive power on ex vivo drug sensitivityii) Functional features predict PFS in patients with R/R CLL treated with ibrutinib + venetoclax, warranting clinical validation also for frontline treatment of CLL."

Clinical • IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • CD8 • IGH • PLCG2

A real-world pharmacovigilance assessment of drug-related carcinoembryonic antigen increase. (PubMed, Medicine (Baltimore)) - "And dacomitinib, regorafenib, fruquintinib, vandetanib, and panitumumab were the top 5 drugs with high risk. Non-antitumor drugs were all moderate risk, involving atorvastatin, zoledronic acid, amiodarone hydrochloride, lithium, and teduglutide...The number of related adverse event reports increased year by year. The results of this study provided the relevant basis for pharmacovigilance, and provided the basis for strengthening drug safety and making correct drug decision in clinical practice."

Adverse events • Journal • Real-world evidence • Oncology • CEACAM5

Extracellular vesicle-associated transcriptomic and proteomic biomarkers show in vitro potential for vandetanib treatment monitoring in anaplastic thyroid cancer. (PubMed, Sci Rep) - "This transcriptional biomarker signature can distinguish vandetanib treatment from control in cell-free RNA isolated from Cal62 EVs and can be measured reliably, easily, and quickly using RT-qPCR. Our findings may serve as a basis for future clinical trials with liquid biopsy samples from ATC patients undergoing off-label vandetanib treatment."

Journal • Preclinical • Oncology • Rare Diseases • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma

Design and synthesis of novel 3,5-diphenyl pyrazolines acting as potent EGFR inhibitors with off-target antileukemic effect. (PubMed, Future Med Chem) - "Pyrazolines 5d and 6a revealed broad-spectrum cytotoxic activities and potent EGFR inhibition with IC50 values of 2.30 µM and 1.47 µM, respectively, in comparison to Vandetanib (IC50 = 0.5 µM) and Gefitinib (IC50 = 0.04 µM). According to predictive models of oral bioavailability and drug-likeness, pyrazolines 5d and 6a are expected to be bioavailable and drug-like compounds. Pyrazolines 5d and 6a are novel EGFR inhibitors with a broad-spectrum anti-cancer activity, and 6a has off-target antileukemic effect."

IO biomarker • Journal • Hematological Malignancies • Leukemia • Oncology • BCL2

Patient-Reported Tolerability of Selpercatinib Compared to Cabozantinib/Vandetanib: A Secondary Analysis of the LIBRETTO-531 Randomized-Controlled Trial in RET-Mutant Medullary Thyroid Cancer. (PubMed, Thyroid) - P3 | " This study demonstrated superior PRT for selpercatinib compared with control in patients with RET-mutant MTC, further supporting selpercatinib use as the first-line treatment for patients with advanced RET-mutant MTC. Comparative PRT deserves further adoption as a complement to traditional endpoints in future randomized-controlled trials."

Journal • Dermatology • Fatigue • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

Systemic Therapy for Advanced Thyroid Cancer-New Personalized Options. (PubMed, Drugs) - "Multikinase inhibitors (MKIs) such as sorafenib, lenvatinib, vandetanib and cabozantinib have demonstrated significant improvements in progression-free survival and objective response rates in patients with RR-DTC and MTC...Despite significant progress, management of advanced thyroid cancer remains challenged by drug resistance and toxicity, underscoring the need for ongoing research and innovation. Furthermore, vast improvements are still required to ensure universal access to molecular testing and targeted therapies."

Journal • Review • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • BRAF • NTRK

Intolerance to RET inhibitors in a patient with aggressive sporadic medullary thyroid carcinoma with metastatic infiltration of bone marrow and concurrent acute myeloid leukemia. (ATA 2025) - "Then treated with vandetanib for 18 months until discontinuation for prolonged QTc...Received HiDAC (high-dose cytarabine) plus GO (gemtuzumab ozogamicin) consolidation...Immunotherapy (pembrolizumab) was initiated but MTC progressed after two months. Then transitioned to pralsetinib, but it was held due to severe thrombocytopenia...Development of pancytopenia on selpercatinib in the patient could be an early sign of AML, drug-related adverse effect, or a consequence of MTC infiltration the BM. BM biopsy should be considered in patients with aggressive MTC who develop pancytopenia given that BM infiltration by MTC is rare."

Clinical • IO biomarker • Late-breaking abstract • Metastases • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Thrombocytopenia • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma

A Rare Case of Medullary Thyroid Carcinoma with BRCA2 Genetic Mutation (ENDO 2025) - "Vandetanib and Zoledronic acid were initiated, with a baseline calcitonin of 221.5 pg/mL. Although biopsy is not recommended for TI-RADS 3 nodules under 2.5 cm, we suggest considering it in cases with elevated calcitonin. Our approach enabled early detection and treatment of this rare MTC. Furthermore, identifying rare genetic mutations in sporadic MTC is pivotal for understanding tumor biology, developing future screening biomarkers, and expanding therapeutic options."

Clinical • Endocrine Cancer • Gynecology • Musculoskeletal Pain • Neuroendocrine Tumor • Oncology • Pain • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • BRCA2 • RB1 • RET • TP53

Targeting RET in medullary thyroid cancer. (PubMed, Endocr Relat Cancer) - "Multikinase inhibitors such as vandetanib and cabozantinib were the first few effective inhibitors which have been shown to slow disease progression in the treatment of advanced MTC. In more recent years, these have been followed by highly-selective RET inhibitors selpercatinib and pralsetinib which have made their way into the clinic, demonstrating high efficacy and a more favourable side-effect profile due to their reduction in off-target effects. In spite of these successes, there remains a continued need to develop strategies to overcome treatment resistance."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

Overcoming resistance in RET-altered cancers through rational inhibitor design and combination therapies. (PubMed, Bioorg Chem) - "Traditional multi-kinase inhibitors (MKIs, such as cabozantinib and vandetanib) exhibit significant side effects due to non-selective inhibition of targets like VEGFR, and also suffer from resistance associated with RET mutations (e.g., V804L/M, G810C/S/R), both of which limit their clinical application...To overcome drug resistance, the design strategies of novel inhibitors focus on multi-target inhibition (such as PLM-101 targeting RET/YES1/FLT3, TPX-0046 targeting RET/SRC), structural optimization (such as helical ring derivatives enhancing binding stability), and natural compound screening (such as ZINC series molecules)...For instance, selpercatinib combined with crizotinib can inhibit MET amplification-driven resistance, while arsenic trioxide combined with pralsetinib restores sensitivity by inhibiting the HH-Gli pathway. Current clinical trials show that novel RET inhibitors such as SY-5007 have a significant objective response rate in advanced RET..."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FGFR • FLT3 • MET • RET • STAT1