Lutathera (lutetium Lu 177 dotatate) / Novartis - LARVOL DELTA

Special Track 3 - Oncology & Theranostics Committee - Debate: Will Alpha Therapy be the Main Radionuclide Therapy Approach in the Future? (EANM 2025) - "This has primarily been in the «niche» of gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) based on the phase III Netter-1 trial showing clinical benefit using radiolabeled somatostatin analogs 177Lu-DOTATATE in patients with tumors that express somatostatin receptors. More recently, in the broader context of advanced prostate cancer, following the phase III Vision clinical trial, demonstrating that 177Lu-PSMA-617 (Pluvicto™) prolonged imaging-based progression-free survival (rPFS) and overall survival, when added to standard care in patients with advanced PSMA-positive metastatic castration-resistant prostate cancer...Severe bone marrow and renal toxicity were less common adverse events. However, the widespread adoption of alpha emitters in clinical practice will imply prospective clinical trials with the demonstration of an impact on survival and acceptable toxicity."

Acute Myelogenous Leukemia • Castration-Resistant Prostate Cancer • Dental Disorders • Endocrine Cancer • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Xerostomia • SSTR

EDU 11 - ASTRO/SNMMI Joint Session: Unlocking Success in Radiopharmaceutical Therapy: Collaboration between Radiation Oncology, Nuclear Medicine and Industry (ASTRO 2025) - "session DESCRIPTION Theranostics, a treatment paradigm pairing diagnostic molecular imaging with radiopharmaceutical therapy (RPT), is resurgent, mainly driven by the FDA approvals of 177Lu-dotatate for neuroendocrine tumors and 177Lu-PSMA-617 for prostate cancer. Explain the current practice of modern RPTs and understand the framework for clinical implementation. Develop an understanding of the importance of patient selection and monitoring with molecular imaging."

Endocrine Cancer • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor

Workshop 02 - Moving Beyond the Basics: Implementation of a Radiopharmaceutical Therapy Program (ASTRO 2025) - "Specifically, Radium-223, Lutetium-177 dotatate and Lutetium-177 PSMA-617 will be discussed. Identify clinical indications for RPTs that are currently approved for clinical use. Identify logistical steps and common challenges in implementing RPT use in their own practice."

Oncology

New Horizons: The Evolution of Nuclear Medicine in the Diagnosis and Treatment of Pancreatic Neuroendocrine Tumors-A Case Report. (PubMed, J Clin Med) - "Recurrent disease was treated with somatostatin analogues (SSAs) and [177Lu]Lu-DOTA-TATE peptide receptor radionuclide therapy (PRRT)...This case not only underscores the clinical utility of advanced nuclear imaging but also illustrates the dynamic nature of pancreatic neuroendocrine tumors. The transition from low-grade to high-grade disease highlights the need for further studies on tumor progression mechanisms and the potential role of adjuvant therapies in managing PanNETs."

Journal • Endocrine Cancer • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

Peptide-Drug Conjugates: A New Hope for Cancer. (PubMed, J Pept Sci) - "Only Lutathera remains FDA-approved after Pepaxto's withdrawal, though Pepaxto retains EMA and MHRA approval-highlighting regulatory and technical complexities. Most PDCs target overexpressed receptors (e.g., somatostatin and GnRH), though novel designs like CBX-12 employ alternative strategies...Promising candidates in late-stage trials are highlighted, emphasising their potential to address unmet needs in oncology. By refining targeting precision and payload delivery, next-generation PDCs may expand treatment options for resistant cancers, bridging the gap between biologics and small-molecule therapies."

Journal • Review • Oncology

Risk of bowel ischemia in patients with mesenteric neuroendocrine tumors after treatment with 177Lu-DOTATATE. (PubMed, Endocr Oncol) - "All patients had metastatic small bowel NET with prominent mesenteric mass encasing/obstructing the mesenteric vessels and preexisting symptoms of postprandial abdominal pain. Acute bowel ischemia may be a rare complication of PRRT in patients with mesenteric arterial or venous obstruction from mesenteric metastasis."

Journal • Cardiovascular • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pain • Pancreatic Cancer • Solid Tumor

Potentially fatal crisis after 177Lu-DOTATATE therapy for paraganglioma: a case report with review of literature. (PubMed, Endocr J) - "At the age of 49, he received 131I-MIBG therapy for the recurrence of pheochromocytoma with bone metastasis. In conclusion, while 177Lu-DOTATATE therapy is generally considered safe, our findings underscore the potential risks of fatal crisis after therapy. Careful monitoring of patients with PPGL should be performed after treatment."

Journal • Cardiovascular • Endocrine Cancer • Hematological Disorders • Musculoskeletal Pain • Neuroendocrine Tumor • Oncology • Pain • Solid Tumor • SSTR

Lutathera: “Extension of indication to include the treatment of newly diagnosed, unresectable or metastatic, well-differentiated (G2 and G3), somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) adult patients for LUTATHERA, based on…CAAA601A22301 (NETTER-2)…as a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated.” (European Medicines Agency) - CHMP Final Minutes of the meeting on 24 - 27 Feb 2025: “The committee adopted a 2nd request for supplementary information with a specific timetable”

CHMP • Gastrointestinal Neuroendocrine Tumor • Oncology • Pancreatic Neuroendocrine Tumor

Evaluation of using small volume of interest regions for clinical kidney dosimetry in 177Lu-DOTATATE treatments. (PubMed, EJNMMI Phys) - "The small volume of interest (SV) method can provide absorbed dose estimates comparable to the whole-kidney parenchyma (WKP) method when optimized. Non-filtered images overestimated doses by 1.22, but applying a 5 mm Gaussian filter aligned SV results with the WKP method. Using multiple VOIs improved accuracy, with five 2 mL SVs achieving 8.3%. The SV method provides a less time-consuming alternative to WKP; however, its implementation is recommended to be validated and adjusted against a reference method."

Journal

The Relationship between Liver Metastasis Shrinkage Rate and Quantitative Values in Lu-177 DOTATATE Therapy for Somatostatin Receptor-Positive Neuroendocrine Tumors (ASTRO 2025) - No abstract available

Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

Lu-177-Dotatate (NET) in a Community Based Practice (ASTRO 2025) - No abstract available

Case of the Season: 177Lu-DOTATATE Peptide Receptor Radiotherapy With Acute Dialysis Support in a Patient With Chronic Kidney Disease (CKD). (PubMed, Semin Roentgenol) - No abstract available

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Alpha Peptide Receptor Radionuclide Therapy (PRRT) with the SSTR antagonist 225Ac-DOTA-LM3 as rescue therapy after failure of PRRT with SSTR agonists/conventional treatment options in neuroendocrine neoplasm G3 (remote) (SNMMI 2025) - "Hydration, premedication (antiemetics/dexamethasone) and para-aminohippuric acid for renal protection were provided during each cycle...Previous PRRT included: 177Lu-DOTATATE (n=7, 58%), 177Lu-DOTATOC (n=5, 42%), 90Y-DOTATOC (n=3, 25%), 90Y-DOTATATE (n=1, 8%), intra-arterial liver administration of 177Lu-DOTATATE or 90Y-DOTATOC (n=1 each, 8%)... Our retrospective analysis shows that α-PRRT with the SSTR antagonist 225Ac-DOTA-LM3 is well-tolerated with a favorable long-term safety profile. In patients with advanced NEN G3 failing standard treatments, including PRRT with SSTR agonists, and no other therapeutic options, promising survival outcomes and very encouraging efficacy results were achieved. Efficacy and survival were comparable with those in a NEN G2 cohort treated under the same conditions."

Acute Myelogenous Leukemia • Anemia • Colorectal Cancer • Endocrine Cancer • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Neuroendocrine Tumor • Oncology • Pain • Pancreatic Cancer • Solid Tumor • Thrombocytopenia • SSTR

Feasibility of Single Time Point Dosimetry Application in 177Lu-DOTATATE/DOTATOC-treated Pediatric Neuroblastoma. (PubMed, Clin Nucl Med) - "The findings confirm that the 96 hours STPH method can reliably replace MTP for dosimetric assessment in pediatric NB patients treated with 177Lu-DOTATATE and performed well in renal dosimetry for 177Lu-DOTATOC therapy."

Journal • Neuroblastoma • Oncology • Pediatrics • Solid Tumor

Somatostatin analogue continuation upon progression in patients with gastroenteropancreatic neuroendocrine tumour (SAUNA trial): a randomised controlled trial protocol. (PubMed, BMJ Open) - P4 | "Second-line treatment options include targeted therapy (everolimus or sunitinib), or peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. Results of the study will be published in peer-reviewed international journals and presented at international conferences. NCT05701241."

Clinical protocol • Journal • Endocrine Cancer • Gastrointestinal Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

Breaking New Ground: First Use of Peptide Receptor Radionuclide Therapy (Prrt) for Metastatic Medullary Thyroid Carcinoma in the Philippines - A Case Report (ENDO 2025) - "Patient underwent total thyroidectomy with right radical neck dissection, and was maintained with Levothyroxine...Given the reduction in calcitonin levels and the absence of disease progression, the patient was advised to undergo an additional cycle of Lutetium-177 DOTATATE therapy. This case highlights the importance of multidisciplinary approach and advanced therapeutic intervention on the management of metastatic MTC. This case highlights the importance of multidisciplinary approach and advanced therapeutic intervention on the management of metastatic MTC. The patient demonstrated a favorable response as evidenced by decreased calcitonin levels and stable disease, indicating that PRRT can provide effective disease control in metastatic MTC. This case also underscores the potential role of the emerging therapies in improving outcomes for patients with advanced MTC."

Case report • Clinical • Metastases • Endocrine Cancer • Gastrointestinal Disorder • Oncology • Otorhinolaryngology • Pulmonary Disease • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • SSTR

Young Onset Metastatic Pheochromocytoma: A Case Report of Clinical and Social Challenges (ENDO 2025) - "Treatment included alpha and beta blockade, surgical resection of the brain lesion, radiation therapy to bony and hepatic lesions, Zoledronic acid for bone metastasis, and chemotherapy (Cyclophosphamide, Vincristine, Dacarbazine)...Additional treatment with Lutathera and Cabozantinib was suggested but delayed due to cost and need for manufacturer assistance...Second, the case reveals the limitations of current available treatments for metastatic PCC, even when specific genetic mutations are identified. And third, the case underscores how social determinants of health can significantly impact patient care and outcomes."

Case report • Clinical • Metastases • Endocrine Cancer • Hepatology • Liver Failure • Musculoskeletal Diseases • Neuroendocrine Tumor • Oncology • Orthopedics • Palliative care • Solid Tumor • NF1 • TERT

Assessing the Effect of Somatostatin Therapy on Glucose Control During Treatment For Neuroendocrine Tumors (ENDO 2025) - "47 patients received concomitant lutate therapy... Twenty patients (29.4%) had pre-existing diabetes prior to SSA commencement. Of these patients, 16 (80%) demonstrated worsening glucose control during SSA therapy. 3 patients remained stable and 1 patient did not have documented BGL monitoring."

Carcinoid Syndrome • Diabetes • Endocrine Cancer • Metabolic Disorders • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor

Testing Lutetium Lu 177 Dotatate in Patients With Somatostatin Receptor Positive Advanced Bronchial Neuroendocrine Tumors (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Apr 2032 ➔ Jan 2033

Trial completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • SSTR

Imaging-derived biomarkers from 68Ga-DOTATOC PET/CT scans to predict survival of patients with neuroendocrine tumors after PRRT with 177Lu-DOTATATE. (PubMed, Cancer Imaging) - "Quantification of 68Ga-DOTATOC PET/CT-derived parameters offers limited prognostic value for OS in NET patients who are receiving PRRT in clinical practice. These findings might emphasize the current robust integration of imaging in clinical decision-making for NET management."

Biomarker • Journal • Retrospective data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor

Postmarketing safety surveillance of 177Lu-DOTA-TATE (LUTATHERA): an observational, pharmacovigilance study leveraging FAERS database. (PubMed, Nucl Med Commun) - "This study enhances understanding of LUTATHERA's safety profile, offers clinicians valuable data, and advocates continuous pharmacovigilance. Continuous pharmacovigilance and potential label updates are recommended."

Adverse events • Journal • P4 data • Cardiovascular • Endocrine Cancer • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Neuroendocrine Tumor • Oncology • Solid Tumor • Thrombocytopenia

Testing Lutetium Lu 177 Dotatate in Patients With Somatostatin Receptor Positive Advanced Bronchial Neuroendocrine Tumors (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2025 ➔ Apr 2032 | Trial primary completion date: Jul 2025 ➔ Apr 2032

Trial completion date • Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • SSTR

Use of the novel cell division assay (CDA) to evaluate T cell toxicity in response to lutetium-177–DOTATATE peptide receptor radionuclide therapy (EACR 2025) - "The CDA could measure the in vitro sensitivity of T cells to 177Lu-DOTATATE and may be a useful tool for evaluating individualized hematological toxicity."

Endocrine Cancer • Immunology • Neuroendocrine Tumor • Oncology • Solid Tumor

Integrating Radiomic Features and Graph Neural Networks for Single Time-Point Dosimetry in Lu-177 PSMA Therapy (SNMMI 2025) - "The GNN-based STP method demonstrated the lowest NRMSE and MAE (0.02455, 0.2597) across all dose cycles, outperforming STP-M (0.0296, 0.3135) and STP-H (0.0457, 0.4841). Fig 2. highlights the performance of STP-GNN compared to the conventional methods STP-M and STP-H across the 8 OARs."

Oncology • Prostate Cancer • Solid Tumor

DOTATATE kinetic rate constant from dynamic 64Cu PET/CT (SNMMI 2025) - "In most cases, the 2T4K (reversible model) was observed to provide a best fit of the data, although an irreversible model was seen to fit the tumors relatively well. Generally good agreement is obtained for the K1 parameter across models. The analysis allowed to distinguish the vascular fraction (VB) from tracer incorporation rate K1."

Oncology