Lutathera (lutetium Lu 177 dotatate)

Our exploratory analysis provides preliminary results showing that imaging indices of inter- and intra-tumor heterogeneity from pretreatment PET/CT images may potentially predict treatment efficacy in NET patients undergoing [177Lu]Lu-DOTA-TATE therapy. However, prospective evaluation in a larger cohort is needed to further assess whether a comprehensive characterization of tumor heterogeneity within a patient can help guide treatment decisions.

Peptide receptor radionuclide therapy (PRRT) using [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE) represents an established treatment modality for somatostatin receptor-positive, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NET) of grade 1 or 2...The results of these studies are likely to help address existing knowledge gaps in the coming years. This review describes the clinical practice, recent developments and future treatment options of PRRT in patients with grade 1 and 2 GEP NET.

The NETseq ensemble classifier identified PRRT-naïve GEP-NETs with high accuracy (≥92%) and demonstrated a potential role in early treatment response monitoring in the PRRT setting. This blood-based, non-invasive, multi-analyte molecular method could be developed as a valuable adjunct to conventional methods in the detection and treatment response assessment in NET patients.

Potential high-risk factors in order to treat effectively and prevent these toxicities in NET patients are presented including the management strategy. This review also discusses novel insights, perspectives, and recent advancements in predicting, preventing, and managing toxicity associated with PRRT, while offering prospective future research directions to minimize clinical toxicity and maximize the therapeutic benefits of PRRT as a treatment strategy for NET patients.

P1/2, N=65, Recruiting, Nationwide Children's Hospital | Trial primary completion date: Nov 2025 --> Nov 2027

The prototype molecular theranostic is the 68Ga/177Lu DOTATATE pair that targets somatostatin receptor subtype 2 in neuroendocrine tumors...Despite challenges and limitations, molecular theranostics is a powerful tool in the precision medicine landscape. Molecular theranostics is a vehicle for improved outcomes in cancer patients with a future-facing portfolio of opportunities.

P1, N=25, Not yet recruiting, University of Chicago

P1/2, N=0, Withdrawn, University of Chicago | N=52 --> 0 | Trial completion date: Feb 2027 --> Sep 2024 | Recruiting --> Withdrawn | Trial primary completion date: Feb 2027 --> Sep 2024

Question Peptide receptor radionuclide therapy is utilised for patients with somatostatin receptor-positive well-differentiated neuroendocrine tumours; however, prognostic predictors are not well established. Findings Progression-free survival was significantly associated with the proportional change in whole tumour volume and total receptor expression between basal and interim [68Ga]Ga-DOTA-TOC PET/CT. Clinical relevance Interim [68Ga]Ga-DOTA-TOC PET/CT can serve as a valuable imaging method to predict prognosis of peptide receptor radionuclide therapy.

P2, N=30, Recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P2, N=25, Recruiting, Fundación de investigación HM | Not yet recruiting --> Recruiting

PRRT utilizes [177Lu]Lu-DOTA-TATE to target the SSR receptor and can significantly prolong progression-free survival in patients with advanced, progressive neuroendocrine tumor of the gastroenteropancreatic system (GEP-NET)...Variable follow-up intervals are recommended for NET G1 and G2. Tumors with higher proliferation rates or advanced metastatic disease necessitate more frequent assessments.

P1, N=10, Recruiting, University of Wisconsin, Madison | Not yet recruiting --> Recruiting

P=N/A, N=80, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Initiation date: Sep 2024 --> Dec 2024

18F-FDOPA PET/CT was found to be the superior functional imaging modality, with 100% lesion detection rate when compared to that of 68Ga-DOTATATE, 18F-FDG, 18F-FDA, and 123I-MIBG scans. While patients did not respond to chemotherapy or tyrosine kinase inhibitors, they responded to targeted radiotherapy using high-specific-activity 131I-MIBG (Azedra®) or 177Lu-DOTATATE (Lutathera®).

Upon enrollment, the patient received two rounds of the radiolabeled somatostatin analogue lutetium-177 octreotate (177Lu-DOTATATE), which was well tolerated...The observed variation in SSTR2 expression between tumor lesions suggests that heterogeneous target expression may have been the reason for treatment failure in this patient's case. Further investigation within the LuDO-N trial will give a more comprehensive understanding of the correlation between SSTR2 expression levels and treatment outcomes, which will be important to advance treatment strategies based on MRT for children with high-risk NB.

P=N/A, N=11, Not yet recruiting, Central Hospital, Nancy, France

P=N/A, N=25, Not yet recruiting, Central Hospital, Nancy, France | Trial completion date: Jul 2024 --> Mar 2025 | Initiation date: Jul 2024 --> Nov 2024 | Trial primary completion date: Jul 2024 --> Jan 2025

P2, N=25, Not yet recruiting, Fundación de investigación HM

P2, N=618, Active, not recruiting, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori | Unknown status --> Active, not recruiting | Trial completion date: May 2021 --> Jan 2025 | Trial primary completion date: May 2021 --> Jan 2025

P1, N=10, Recruiting, Stanford University | Trial primary completion date: Mar 2024 --> Mar 2025

P2, N=130, Recruiting, National Cancer Institute (NCI) | N=90 --> 130

Carcinoid crisis is a rare but potentially life-threatening complication of Lutetium-177-Dotatate therapy. Knowledge of risk factors and prompt recognition of symptoms is essential to successful treatment, with early initiation of intravenous octreotide serving a critical step in reducing morbidity of this adverse event.

P1/2, N=200, Recruiting, Novartis Pharmaceuticals | Trial completion date: May 2028 --> Jun 2029 | Trial primary completion date: May 2025 --> Jun 2029

After prostate biopsy revealed neuroendocrine prostate cancer (NEPC), he was treated with platinum-based systemic chemotherapy followed by pembrolizumab treatment. Subsequently, the primary tumor regressed remarkably, and the urethral catheter was removed. 177Lu-DOTATATE peptide receptor radionuclide therapy may be an effective option for tNEPC, which has few effective treatment options.

P2, N=275, Active, not recruiting, CHU de Quebec-Universite Laval | Recruiting --> Active, not recruiting

From October 2009 to October 2021, 42 meningioma patients with radiologic recurrence after standard therapies were treated with 90Y-DOTATOC (dosage of 1.1 or 5.5 GBq) or with 177Lu-DOTATATE (dosage of 3.7 or 5.5 GBq) in a mean of 4 cycles...Furthermore, PRRT could represent a potential retreatment option. Further studies, also in combination with other treatments, are warranted.

Hydroxyurea, gemcitabine and triapine all increased cell size, SSTR2A expression, and [177Lu]Lu-DOTA-TATE uptake, whilst reducing cell metabolic viability in U2OS + SSTR2A cells when compared to [177Lu]Lu-DOTA-TATE monotherapy. Further investigations could transform patient care and positively increase outcomes for patients treated with [177Lu]Lu-DOTA-TATE.

P=N/A, N=89, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P2; Not yet recruiting --> Recruiting | Trial completion date: Dec 2028 --> Mar 2029 | Trial primary completion date: Mar 2028 --> Sep 2028

Tumour burden at baseline showed no predictive value of PFS/OS after PRRT in this small retrospective study. An increase of tumour burden was predictive of worse outcome.

P1, N=36, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

Patients treated with 177Lu-DOTATATE showed a significant improvement in liver function and cholestasis parameters, and a consistent decrease in bone marrow function, even in the presence of advanced liver disease.

Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTA-TATE has recently been evaluated for the treatment of meningioma patients...Our patient-derived meningioma culture model can be used to assess the short-term response to PRRT and EBRT in radiobiological studies. Further improvement of this model should pave the way towards the development of a relevant culture model for assessment of the long-term response to radiation and, potentially, individual patient responses to PRRT and EBRT.

P3, N=196, Active, not recruiting, Sinotau Pharmaceutical Group | Recruiting --> Active, not recruiting

The tumor AD that was reported during treatment with 177Lu-SSTR-RT in refractory meningioma patients is generally low. Harmonization of the methodology for dosimetry calculations is needed to compare the different reported values and optimize treatment at the individual level.

P4, N=6, Recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Feb 2028 --> May 2028

Image-based features such as SSTR-avid tumor volume, bone tumor involvement, and the presence of large tumors with low SSTR expression demonstrated significant predictive value for PFS, suggesting potential clinical utility in NETs management. Moreover, elevated CgA and ALP, along with an increased number of prior systemic treatments, emerged as significant factors associated with worse PRRT outcomes.

P2, N=18, Suspended, Weill Medical College of Cornell University | Recruiting --> Suspended

P=N/A, N=80, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2029 --> Aug 2029 | Initiation date: May 2024 --> Aug 2024 | Trial primary completion date: May 2028 --> Aug 2028

P2, N=120, Recruiting, University of Iowa | Not yet recruiting --> Recruiting | Trial completion date: Mar 2029 --> Dec 2029 | Trial primary completion date: Jan 2029 --> Dec 2029

P2, N=32, Active, not recruiting, NYU Langone Health | Recruiting --> Active, not recruiting | Trial completion date: May 2025 --> Feb 2026 | Trial primary completion date: May 2024 --> Feb 2025