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BACKGROUND: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolonged life in patients with metastatic castration-resistant prostate cancer (mCRPC) in VISION (NCT03511664). However, distinguishing between patients likely and unlikely to respond remains a clinical challenge. We present the first multivariable models of outcomes with 177Lu-PSMA-617 built using data from VISION, a large prospective phase 3 clinical trial powered for overall survival. METHODS: Adults with progressive post androgen receptor pathway inhibitor and taxane prostate-specific membrane antigen (PSMA)-positive mCRPC received 177Lu-PSMA-617 plus protocol-permitted standard of care (SoC) or SoC alone. In this post hoc analysis, multivariable Cox proportional hazards models of overall survival (OS) and radiographic progression-free survival (rPFS), and a logistic regression model of prostate-specific antigen response (≥50% decline; PSA50) were constructed and evaluated using C-index or receiver operating characteristic (ROC) analyses with bootstrapping validation. Nomograms were constructed for visualisation. FINDINGS: Patients were randomised between June 2018 and October 2019. Data from all 551 patients in the 177Lu-PSMA-617 arm were analysed in multivariable modelling. The OS nomogram (C-index, 0.73; 95% confidence interval [CI], 0.70-0.76) included whole-body maximum standardised uptake value (SUVmax), time since diagnosis, opioid analgesic use, aspartate aminotransferase, haemoglobin, lymphocyte count, presence of PSMA-positive lesions in lymph nodes, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and neutrophil count. The rPFS nomogram (C-index, 0.68; 0.65-0.72) included SUVmax, time since diagnosis, opioid analgesic use, lymphocyte count, presence of liver metastases by computed tomography, LDH, and ALP. The PSA50 nomogram (area under ROC curve, 0.72; 95% CI, 0.68-0.77) included SUVmax, lymphocyte count and ALP. Performances of the OS and rPFS models were maintained when they were reconstructed excluding SUVmax. INTERPRETATION: These models of outcomes with 177Lu-PSMA-617 are the first built using prospective phase 3 data. They show that a combination of pretreatment laboratory, clinical, and imaging parameters, reflecting both patient and tumour status, influences outcomes. These models are important for aiding treatment selection, patient management, and clinical trial design. FUNDING: Novartis.

Important progress has been made over the last decade in the classification, imaging, and treatment of neuroendocrine neoplasm (NENs), with several new agents approved for use. Although the treatment options available for patients with well-differentiated neuroendocrine tumors (NETs) have greatly expanded, the rapidly changing landscape has presented several unanswered questions about how best to optimize, sequence, and individualize therapy. Perhaps the most important development over the last decade has been the approval of 177Lu-DOTATATE for treatment of gastroenteropancreatic-NETs, raising questions around optimal sequencing of peptide receptor radionuclide therapy (PRRT) relative to other therapeutic options, the role of re-treatment with PRRT, and whether PRRT can be further optimized through use of dosimetry among other approaches. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trial planning meeting in 2021 with multidisciplinary experts from academia, the federal government, industry, and patient advocates to develop NET clinical trials in the era of PRRT. Key clinical trial recommendations for development included 1) PRRT re-treatment, 2) PRRT and immunotherapy combinations, 3) PRRT and DNA damage repair inhibitor combinations, 4) treatment for liver-dominant disease, 5) treatment for PRRT-resistant disease, and 6) dosimetry-modified PRRT.

High-grade neuroendocrine neoplasms are a rare disease entity and account for approximately 10% of all neuroendocrine neoplasms. Because of their rarity, there is an overall lack of prospectively collected data available to advise practitioners as to how best to manage these patients. As a result, best practices are largely based on expert opinion. Recently, a distinction was made between well-differentiated high-grade (G3) neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas, and with this, pathologic details, appropriate imaging practices and treatment have become more complex. In an effort to provide practitioners with the best guidance for the management of patients with high-grade neuroendocrine neoplasms of the gastrointestinal tract, pancreas, and gynecologic system, the North American Neuroendocrine Tumor Society convened a panel of experts to develop a set of recommendations and a treatment algorithm that may be used by practitioners for the care of these patients. Here, we provide consensus recommendations from the panel on pathology, imaging practices, management of localized disease, management of metastatic disease and surveillance and draw key distinctions as to the approach that should be utilized in patients with well-differentiated G3 neuroendocrine tumors vs poorly differentiated neuroendocrine carcinomas.

The field of radionuclide therapy (RNT) for prostate cancer (PC) is growing rapidly, with recent Food and Drug Administration approval of the first 177Lu-PSMA ligand. We aimed to develop the first patient-reported outcome (PRO) measure for PC patients receiving RNT. Methods: We identified relevant symptoms and toxicities by reviewing published trials and interviews with PC patients receiving RNT (n = 29), caregivers (n = 14), and clinicians (n = 11). Second, we selected items for measure inclusion. Third, we refined the item list with input from experts in RNTs and PROs. Fourth, we finalized the Functional Assessment of Cancer Therapy-Radionuclide Therapy (FACT-RNT) with patient input. Results: This multistep process yielded a brief 15-item measure deemed by key stakeholders to be relevant and useful in the context of RNT for PC. Conclusion: The FACT-RNT is a new standardized tool to monitor relevant symptoms and toxicities among PC patients in RNT trials and real-world settings.

We report the impact of 177Lu DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors (NETs) often find burdensome. Methods: All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial (177Lu-DOTATATE plus standard-dose octreotide long-acting repeatable [LAR], n = 117; high-dose octreotide LAR, n = 114) were asked to record the occurrence of predefined symptoms in a daily diary. Change from baseline in symptom scores (mean number of days with a symptom) was analyzed using a mixed model for repeated measures. Results: Patients (intent-to-treat) who received 177Lu-DOTATATE experienced a significantly greater decline from baseline in symptom scores than patients who received high-dose octreotide LAR. For 177Lu-DOTATATE, the mean decline in days with abdominal pain, diarrhea, and flushing was 4.10, 4.55, and 4.52 days per 4 weeks, respectively, compared with 0.99, 1.44, and 2.54 days for high-dose octreotide LAR. The mean differences were 3.11 days (95% confidence interval, 1.35-4.88; P = 0.0007) for abdominal pain, 3.11 days (1.18-5.04; P = 0.0017) for diarrhea, and 1.98 days (0.08-3.88; P = 0.0413) for flushing, favoring 177Lu-DOTATATE. A positive repeated measures correlation was found between diary-recorded symptom scores and questionnaire-recorded pain, diarrhea, and flushing. Conclusion: In addition to efficacy and quality of life benefits, symptom diaries from NETTER-1 demonstrated that treatment with 177Lu DOTATATE was associated with statistically significant reductions in abdominal pain, diarrhea, and flushing, constituting the core symptoms of patients with progressive midgut NETs, compared with high-dose octreotide LAR, supporting a beneficial effect of 177Lu DOTATATE on HRQoL.

Current treatment options for patients with unresectable locally advanced pancreatic cancer (LAPC) include chemotherapy alone or followed by chemoradiation or stereotactic body radiotherapy. However, the prognosis for these patients remains poor, with a median overall survival

Simple Summary: Peptide receptor radionuclide therapy using 177Lu-DOTATATE is a standard therapy for patients with metastatic neuroendocrine tumors. Many patients with liver-dominant disease undergo liver embolization as an earlier line of treatment. It is unclear whether prior embolization impacts the safety and efficacy of subsequent 177Lu-DOTATATE treatment. We analyzed 171 patients who underwent treatment with 177Lu-DOTATATE, among whom 61 underwent prior embolization. There was no significant difference in serious liver toxicity or radiographic progression of liver tumors between the group that had undergone prior embolization and the group that had not. The conclusion is that peptide receptor radionuclide therapy with 177Lu-DOTATATE in patients who had prior liver embolization is both safe and effective. Rationale: Evaluating the long-term safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumors (mNETs) who have undergone prior bland hepatic transarterial embolization (TAE). Methods: Retrospective review of mNET patients who received PRRT with 177Lu-DOTATATE between 4/2018 and 02/2022 with and without prior TAE. The most recent clinical, imaging, and laboratory findings, including hepatic Common Terminology Criteria for Adverse Events v5.0, were compared to pre-PRRT. Results: 171 patients (95 M, 76 F, median age = 66) with mNET of different primary sites (9 foregut, 100 midgut, 9 hindgut, 44 pancreas, 9 unknown) received at least 1 cycle of PRRT with at least 6 months of follow-up, 110 of whom were embolization-naïve and 61 who had prior TAE. The median follow up was 22 months (range: 6–43). Patients with prior TAE had higher liver tumor burden on average than patients without prior TAE; however, the difference was not statistically significant (p = 0.06). There was no significant difference in the rates of G3 or G4 hepatotoxicity (p = 0.548 and p = 0.999, respectively) in patients who underwent prior TAE and those who were TAE-naïve. The hepatic progression-free survival was 22.9 months in TAE-naïve patients and 25.7, 20.2, and 12.8 months in patients with 1, 2, and 3 prior TAE treatments, respectively. Conclusion: Peptide receptor radionuclide therapy following transarterial bland embolization for mNET is safe and effective. [ABSTRACT FROM AUTHOR]