First multicentric randomized phase II trial investigating the antitumor efficacy of peptide receptor radionuclide therapy with 177Lutetium – Octreotate (OCLU) in unresectable progressive neuroendocrine pancreatic tumor: Results of the OCLURANDOM trial, on behalf of the ENDOCAN RENATEN network and GTE

Background: Given the rarity and heterogeneity of pancreatic neuroendocrine neoplasms (pNEN), treatment algorithms and sequencing are primarily guided by expert opinions with limited evidence. Aim: To investigate overall survival (OS), median progression-free survival (mPFS), and prognostic factors associated with the most common medical treatments for pNEN. Methods: Retrospective single-center study encompassing patients diagnosed and monitored between 2000 and 2020 (n = 192). Results: Median OS was 36 (95% CI: 26–46) months (99 months for grade (G) 1, 62 for G2, 14 for G3, and 10 for neuroendocrine carcinomas). Patients treated with somatostatin analogues (SSA) (n = 59, median Ki-67 9%) had an mPFS of 28 months. Treatment line (HR (first line as reference) 4.1, 95% CI: 1.9–9.1, p ≤ 0.001) emerged as an independent risk factor for time to progression. Patients with a Ki-67 index ≥10% (n = 28) had an mPFS of 27 months. Patients treated with streptozocin/5-fluorouracil (STZ/5FU) (n = 70, first-line treatment n = 68, median Ki-67 10%) had an mPFS of 20 months, with WHO grade serving as an independent risk factor (HR (G1 (n = 8) vs. G2 (n = 57)) 2.8, 95% CI: 1.1–7.2, p-value = 0.031). Median PFS was 21 months for peptide receptor radionuclide therapy (PRRT) (n = 41, first line n = 2, second line n = 29, median Ki-67 8%), 5 months for carboplatin and etoposide (n = 66, first-line treatment n = 60, median Ki-67 80%), and 3 months for temozolomide-based therapy (n = 56, first-line treatment n = 17, median Ki-67 30%). Conclusion: (1) Overall survival was, as expected, highly dependent on grade; (2) median PFS for SSA was around 2.5 years without difference between tumors with Ki-67 above or below 10%; (3) STZ/5FU as first-line treatment exhibited a superior mPFS of 20 months compared to what has historically been reported for targeted treatments; (4) PRRT in G2 pNEN achieved an mPFS similar to first-line chemotherapy; and (5) limited treatment efficacy was observed in high-grade tumors when treated with carboplatin and etoposide or temozolomide.

Section: Discussionmentioning

confidence: 99%

Responses to Medical Treatment in 192 Patients with Pancreatic Neuroendocrine Neoplasms Referred to the Copenhagen Neuroendocrine Tumour Centre in 2000–2020

Petersen,

Møller,

Slott

et al. 2024

“…Initial results showed 80% of patients without disease progression in 12 months in the PRRT arm. The median PFS estimated is 20.7 (17.2–23.7) months for PRRT versus 11.0 (8.8–12.4) months with sunitinib [ 12 ]. These preliminary results on pancreatic NETs go toward our hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Survival and Response Outcomes for Gastrointestinal Neuroendocrine Tumor (GEP-NETs) Patients Treated with Lutetium—177-DOTATATE in a Brazilian Reference Center: A Six-Year Follow-Up Experience

de Souza,

Xavier,

Gomes

et al. 2023

Background: PRRT can be an option for all-grade GEP-NETs, but selecting patients is challenging. In this scenario, clinical-pathological and radiological characteristics, such as pre-treatment Ga-68 DOTA PET/CT, might have the potential to help. Methods: A retrospective chart review was conducted on advanced GEP-NETs treated with at least one PRRT dose. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan–Meier method. Krenning Score (KS), and the maximum standardized uptake value (SUVmax) were derived from the pre-treatment scans. A maximally selected rank statistics test was used for SUVmax simple cut point estimate. Results: Among 36 patients, 19 had primary pancreatic tumors. The numbers of G1, G2, and G3 tumors were 10, 18, and 7, respectively. During a median follow-up of 90.5 months, 4 patients died. Median OS was not reached for G1 and G2 tumors, and it was 30 months for G3 (p = 0.001). Median PFS was 23 months, with G3 showing lower PFS compared to G1 [7 versus 30 months; HR 8.41 (95%CI 2.2–31.0; p = 0.001)]. Conclusions: PRRT provides long-term PFS in patients with G1/G2 GEP-NETs independent of clinical characteristics and primary site. G3 has worse survival, but selected patients may experience long OS after PRRT treatment.

“…Among the different second-line options in well-differentiated panNETs, 177 Lu-DOTATATE seems to compare favorably to targeted therapy (everolimus or sunitinib) or chemotherapy [ 69 ]. In the randomized phase II OCLURANDUM trial, PRRT with 177 Lu-DOTATATE was associated with a higher median PFS of 20.7 months compared to 11.0 months for sunitinib treatment in patients with advanced, SSTR-positive, progressive panNET [ 70 ]. Currently, the randomized phase III COMPETE trial is comparing PRRT with 177 Lu-edotreotide with everolimus in advanced, progressive GEP-NET patients.…”

Section: Patient Selectionmentioning

confidence: 99%

A Clinical Guide to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in Neuroendocrine Tumor Patients

Becx

Minczeles

Brabander

et al. 2022

Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-[DOTA0,Tyr3]-octreotate (177Lu-DOTATATE) has become an established second- or third-line treatment option for patients with somatostatin receptor (SSTR)-positive advanced well-differentiated gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). Clinical evidence of the efficacy of PRRT in tumor control has been proven and lower risks of disease progression or death are seen combined with an improved quality of life. When appropriate patient selection is performed, PRRT is accompanied by limited risks for renal and hematological toxicities. Treatment of NET patients with PRRT requires dedicated clinical expertise due to the biological characteristics of PRRT and specific characteristics of NET patients. This review provides an overview for clinicians dealing with NET on the history, molecular characteristics, efficacy, toxicity and relevant clinical specifics of PRRT.