Emerging Data Support Dose Escalation in Patients with Neuroendocrine Tumors

In the treatment of patients with neuroendocrine tumors (NETs), somatostatin analogs (SSA) and octreotide long-acting release (LAR) are often used in clinical studies. In patients with uncontrolled symptoms or disease progression, individualized dose escalation or interval shortening of SSA can be adjusted. Studies such as the NETTER-1 (NCT01578239)¹ and NETTER-2 (NCT03972488)² trials support dose escalation.

In an interview at the 2025 North American Neuroendocrine Tumor Society (NANETS) Symposium, Jennifer Chan, MD, MPH, NANETS president and associate professor of medicine at Harvard Medical School, discussed dose escalation in NETs and the relationships between NANETS, ENETS, and research groups.

Targeted Oncology®: How does the collaboration between ENETS and NANETS impact clinical trial development and research?

Jennifer Chan, MD, MPH: We have a growing collaboration at the North American Neuroendocrine Tumor Society [NANETS] with our colleagues in Europe who are part of the European Neuroendocrine Tumor Society [ENETS], and I think the collaboration and the interactions have really helped us to foster communication about some of the research questions that are of mutual interest, some of the challenges that we face, and strategies that we can share to overcome some of these issues.

What role do research groups such as SPORE play in the development of novel therapeutic strategies in treating NETs?

Our keynote address at the meeting today was given by Dr Dawn Quelle. She’s one of the co-leads at the Iowa SPORE, Specialized Program of Research Excellence. There’s 1 in the US that is being conducted at the Iowa program. And these have been really fundamental for answering basic science questions and including clinical research to identify new strategies that can ultimately, I think, inform our understanding of [NETs] and potential novel therapies.

What new data support individualized dose escalation or interval shortening of somatostatin analogs in patients with uncontrolled symptoms or disease progression?

We often will adjust the dose of [SSA], either increase the dose of octreotide [long-acting release] LAR from the standard dose of 30 mg, even 40 mg or 60 mg, if there are uncontrolled symptoms of carcinoid syndrome. Sometimes that dose escalation can help minimize the symptoms of, for instance, flushing and diarrhea.

There has been some information also from clinical trials, not randomized trials, but the control arms from, for instance, the NETTER-1 trial and the NETTER-2 trial, that suggest that even in patients who might have higher grade disease—for instance, in the NETTER-2 trial, or patients who may have progressed after standard dose [SSA] as was the case in the NETTER-1 trial—that there may be some period of disease control by just increasing from 30 mg to 60 mg of octreotide LAR.

There also was a phase 2 trial that showed that lanreotide [Somatuline Depot], another [SSA], if you shorten the interval from the usual 120 mg every 4 weeks to 120 mg every 2 weeks, that patients who had progressed on standard dose again might achieve some progression-free survival with the dose escalation. We’re awaiting the results from the SORENTO (NCT05050942)³ trial, which is looking at a novel, highly bioavailable formulation of octreotide, a self-administered formulation that also will be addressing the issue of whether dose and bioavailability matter. In that particular trial, patients were randomly assigned to receive CAM2029, this novel version of octreotide, compared with standard-dose octreotide or lanreotide. We will know from that trial whether that formulation, which is more bioavailable, may have superior efficacy to standard dosing.

What factors should guide a decision to intensify or switch SSA therapy, and how do these strategies align with evolving guideline recommendations?

In clinical practice, we probably most commonly will escalate the dose; for octreotide, either increase from standard 30 mg to 40 mg or 60 mg to help with symptom control. Uncontrolled carcinoid syndrome is probably the most common reason we adjust the dose. The same thing could be said for lanreotide, the 120 mg every 4 weeks, we may give more frequently every 3 weeks or every 2 weeks. That’s mainly for symptom control. So that really is consistent with what’s, for instance, in the [National Comprehensive Cancer Network] guidelines for dose adjustment for symptom control. There’s less controlled data about dose escalation for disease control, but there are some observational results, either from the control arms of the other studies, that suggest to us may achieve some disease control, but we’re awaiting the results of trials to help us understand that better.

REFERENCES:

1. A study comparing treatment with 177Lu-DOTA0-Tyr3-Octreotate to octreotide LAR in patients with inoperable, progressive, somatostatin receptor positive midgut carcinoid tumours (NETTER-1). ClinicalTrials.gov. Updated April 4, 2022. Accessed October 28, 2025. https://clinicaltrials.gov/study/NCT01578239

2. Study to evaluate the efficacy and safety of lutathera in patients with grade 2 and grade 3 advanced GEP-NET (NETTER-2). ClinicalTrials.gov. Updated August 6, 2025. Accessed October 28, 2025. https://clinicaltrials.gov/study/NCT03972488

3. A trial to assess efficacy and safety of octretide subcutaneous depot in patients with GEP-NET (SORENTO). ClinicalTrials.gov. Updated December 13, 2024. Accessed October 28, 2025. https://clinicaltrials.gov/study/NCT05050942