OCLURANDOM: [177Lu]Lu-dota-tate Shows Antitumor Activity in Progressive Metastatic Pancreatic Neuroendocrine Tumors

Patients with metastatic pancreatic neuroendocrine tumors can have very different clinical courses. Treatment decisions often depend on tumor grade, disease burden, symptoms, hormone secretion, and documented progression.

Peptide receptor radionuclide therapy with [177Lu]Lu-dota-tate is an established option for somatostatin receptor-positive neuroendocrine tumors. However, randomized evidence dedicated specifically to metastatic pancreatic neuroendocrine tumors has been limited.

OCLURANDOM evaluated [177Lu]Lu-dota-tate in patients with pretreated, progressive, somatostatin receptor-positive, metastatic pancreatic neuroendocrine tumors, using sunitinib as an internal control.

The original article, titled “[177Lu]Lu-dota-tate versus sunitinib in patients with metastatic progressive neuroendocrine tumours of the pancreas (OCLURANDOM): a randomised, controlled, phase 2 trial,” was published in The Lancet Oncology in June 2026.

Authors: Eric Baudin, Alice Durand, Amandine Beron, Denis Smith, Désirée Déandreis, David Taieb, Catherine Ansquer, Lawrence Dierickx, Emmanuel Deshayes, Olivia Hentic, Salma Moalla, Yves Menu, Rachida Lebtahi, Eric Assenat, Yann Touchefeu, Rosine Guimbaud, Laetitia Dahan, Livia Lamartina, Nadir Cheurfa, Elske Quak, Karine Bouhier-Leporrier, Magalie Haissaguerre, Elif Hindie, Christine Do Cao, Catherine Lombard-Bohas, Arnaud Jannin, Thomas Walter, Michel Ducreux, Sarah Chaib, Julien Hadoux, and Stephanie Foulon.

Why This Study Matters

Advanced pancreatic neuroendocrine tumors have several systemic treatment options, including somatostatin analogues, everolimus, sunitinib, cytotoxic chemotherapy, peptide receptor radionuclide therapy, and cabozantinib. Because patients may live for several years with metastatic disease, treatment sequencing is important. OCLURANDOM adds randomized phase 2 evidence in a dedicated pancreatic neuroendocrine tumor population and provides long follow-up, including data on late adverse events.

Study Design

OCLURANDOM was a randomized, open-label, non-comparative, sunitinib-controlled phase 2 trial conducted at 10 academic centers in France. The trial enrolled adults with sporadic, advanced pancreatic neuroendocrine tumors. Eligible patients had received at least one prior systemic therapy, had somatostatin receptor-positive disease, measurable disease by RECIST 1.1, documented progression within 12 months, ECOG performance status of 0–2, and adequate bone marrow, renal, and hepatic function.

Patients were randomly assigned 1:1 to receive either:

• [177Lu]Lu-dota-tate 7.4 GBq intravenously every 8 weeks for up to 4 cycles, with concomitant amino acid infusion
• sunitinib 37.5 mg orally once daily.

Randomization was stratified by Ki-67, liver involvement, number of previous treatment lines, and previous cytotoxic chemotherapy. The primary endpoint was 12-month progression-free survival, assessed by blinded central review according to RECIST 1.1 in the intention-to-treat population. Secondary endpoints included overall progression-free survival, time to progression, overall survival, objective response, best overall response, duration of response, safety, and quality of life. The trial was registered with ClinicalTrials.gov: NCT02230176.

You can also read about Pancreatic Neuroendocrine Tumors on OncoDaily.

Patient Population

Between February 13, 2015, and July 16, 2020, 84 patients were enrolled.

• 41 patients were assigned to [177Lu]Lu-dota-tate.
• 43 patients were assigned to sunitinib.

The median age was 62.2 years. Overall, 44 patients were women and 40 were men. Most patients had liver metastases, and more than half had received prior cytotoxic chemotherapy. At the data cutoff of April 10, 2024, the median follow-up was 72.5 months.

Treatment Exposure

Patients in the [177Lu]Lu-dota-tate group received treatment for a median duration of 5.6 months, and 36 of 41 patients completed all 4 planned injections. Patients in the sunitinib group received treatment for a median duration of 8.8 months.

Dose reductions were reported in 1 patient in the [177Lu]Lu-dota-tate group and 23 patients in the sunitinib group. Disease progression led to treatment discontinuation in 2 patients in the [177Lu]Lu-dota-tate group and 32 patients in the sunitinib group, while adverse events led to discontinuation in 2 and 9 patients, respectively.

Key Findings

OCLURANDOM met its primary endpoint. At 12 months, 80.5% of patients treated with [177Lu]Lu-dota-tate were alive without disease progression, compared with 41.9% of patients treated with sunitinib. The sunitinib group validated the prespecified control assumption of the trial design, supporting the activity of [177Lu]Lu-dota-tate in this setting.

Median progression-free survival was 20.7 months with [177Lu]Lu-dota-tate and 11.0 months with sunitinib. Median time to progression was 20.7 months with [177Lu]Lu-dota-tate and 11.2 months with sunitinib.

No complete responses occurred in either group. Partial response as best overall response occurred in 63.4% of patients in the [177Lu]Lu-dota-tate group and 30.2% in the sunitinib group.

Objective response at 12 months was 46.3% with [177Lu]Lu-dota-tate and 16.3% with sunitinib. Median duration of response was similar between groups: 15.0 months with [177Lu]Lu-dota-tate and 14.3 months with sunitinib. Responses occurred later with [177Lu]Lu-dota-tate. Median time from randomization to partial response was 8.5 months with [177Lu]Lu-dota-tate and 5.7 months with sunitinib. Median overall survival was 55.8 months in the [177Lu]Lu-dota-tate group and 64.4 months in the sunitinib group, with no statistically significant difference observed in post-hoc analysis.

Overall survival interpretation is limited by subsequent treatment. After progression, 65% of patients initially assigned to sunitinib later received [177Lu]Lu-dota-tate, while 56% of patients initially assigned to [177Lu]Lu-dota-tate later received sunitinib.

Quality of Life and Safety Profile

Quality-of-life outcomes favored [177Lu]Lu-dota-tate during the treatment phase. From baseline to week 48, the mean EORTC QLQ-C30 global health status score was 69.5 with [177Lu]Lu-dota-tate and 59.2 with sunitinib, corresponding to a 10.3-point difference in favor of [177Lu]Lu-dota-tate. Treatment-related side-effect burden, measured with the GI-NET 21 questionnaire, was also lower with [177Lu]Lu-dota-tate than with sunitinib.

During the active treatment phase, grade 3 or 4 adverse events occurred in 44% of patients treated with [177Lu]Lu-dota-tate and 72% of patients treated with sunitinib. The most common grade 3 or 4 events were lymphopenia, nausea, and hypertension with [177Lu]Lu-dota-tate, and neutropenia, leukopenia, diarrhea, fatigue, and hypertension with sunitinib.

Drug-related serious adverse events occurred in 15% of patients in the [177Lu]Lu-dota-tate group and 23% of patients in the sunitinib group. No deaths occurred during the active treatment phase. Late adverse events were also reported with [177Lu]Lu-dota-tate, mainly hematologic and kidney-related. One patient developed myelodysplastic syndrome and later died from acute leukemia, which was classified as related to the investigational drug. These findings support the need for long-term safety monitoring when using [177Lu]Lu-dota-tate in this setting.

Study Limitations

OCLURANDOM was randomized but non-comparative. The sunitinib group served as an internal control to validate the assumptions of the study design, rather than as a formal confirmatory comparator. For this reason, direct comparisons between treatment groups should be interpreted as post-hoc.

Somatostatin receptor scintigraphy was used for eligibility assessment instead of PET imaging, which may have influenced patient selection. The late adverse event analysis was also limited by the small number of evaluable patients in the sunitinib group. Potential baseline imbalances between groups cannot be fully excluded.

Takeaway

OCLURANDOM met its primary endpoint and supports the antitumor activity of [177Lu]Lu-dota-tate in patients with pretreated, progressive, somatostatin receptor-positive, metastatic pancreatic neuroendocrine tumors.

Within this randomized, non-comparative design, the [177Lu]Lu-dota-tate arm showed higher 12-month progression-free survival, longer median progression-free survival, higher response rates, and better quality-of-life measures during treatment.

The long follow-up also highlights the need to consider late hematologic and kidney-related adverse events when sequencing treatment for patients with metastatic pancreatic neuroendocrine tumors.

The full article is available in The Lancet Oncology.