Pending the results of the ongoing phase 3 SORENTO trial (NCT05050942), increasing the dose or shortening the treatment interval of somatostatin analogs may be a viable route to take for patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in need of symptom and/or disease control, according to Jennifer Chan, MD, MPH.
“We’re awaiting the results of the SORENTO trial, which is looking at a novel highly bioavailable formulation of octreotide, a self-administered formulation of octreotide, that will be addressing this issue of whether dose and bioavailability matter,” Chan said in an interview with OncLive® during the 2025 NANETS Multidisciplinary NET Medical Symposium.1,2
“In that trial, patients were randomly assigned to receive CAM2029, this novel version of octreotide, or standard dose octreotide or lanreotide. [Results] from that trial [will inform] whether that formulation, which is more bioavailable [than octreotide or lanreotide], may have superior efficacy to standard dosing,” Chan added.
In the interview, Chan, the clinical director of the Gastrointestinal Cancer Center, director of the Program in Carcinoid and Neuroendocrine Tumors, and an institute physician at Dana-Farber Cancer Institute, and an associate professor of medicine at Harvard Medical School in Boston, Massachusetts, discussed the relationship between dose escalation and symptom control, the evidence that supports potential disease control benefits, and how results from the SORENTO trial could redefine current standards.
Chan’s Topline Takeaways on Optimizing Somatostatin Analog Use in GEP-NETs
- Increasing octreotide LAR to 40 mg or 60 mg or shortening lanreotide intervals can improve control of carcinoid syndrome symptoms like flushing and diarrhea.
- Observational data from trials such as NETTER-1, NETTER-2, and CLARINET FORTE suggest higher doses or shorter dosing intervals may prolong disease stability.
- The ongoing phase 3 SORENTO trial is testing a novel, self-administered, highly bioavailable octreotide that could reshape somatostatin analog dosing paradigms.
OncLive: What new data support individualized dose escalation or interval shortening of somatostatin analogs in patients with uncontrolled symptoms or disease progression?
Chan: We often will adjust the dose of somatostatin analogs either by increasing the dose of octreotide long-acting repeatable [LAR] from the standard dose of 30 mg, [to] 40 mg or 60 mg, if there are uncontrolled symptoms of carcinoid syndrome. Sometimes that dose escalation can help minimize the symptoms of flushing and diarrhea, for instance. We also have information from the control arms from, for instance, the NETTER-1 [NCT01578239] and the NETTER-2 [NCT03972488] trials, 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 somatostatin analog, as was the case in the NETTER-1 trial, that there may be some period of disease control by increasing the dose from 30 mg to 60 mg of octreotide LAR.
There was also the phase 2 CLARINET FORTE trial [NCT02651987] that showed for lanreotide, another somatostatin analog, that if you shorten the interval from the usual 120 mg every 4 weeks to 120 mg every 2 weeks, patients who had progressed on standard dose [therapy] might achieve some progression-free survival benefit with the dose escalation.
What factors should guide the decision to intensify or switch somatostatin analog therapy, and how do these strategies align with evolving guideline recommendations?
In clinical practice, we probably most commonly will escalate the dose. For octreotide, [we’ll either] increase from the standard [dose of] 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, either every 3 weeks or every 2 weeks, mainly for symptom control. That is consistent with what’s in the National Comprehensive Cancer Network guidelines, for instance, for dose adjustment for symptom control. There’s less controlled data about dose escalation for disease control, but there are some observational results from the control arms of other studies that suggest [we] may achieve some disease control, but we’re awaiting the results of trials to help us understand that better.
References
- Dose optimisation of SSAs: the evolving story in GEP-NET management; supported by Camurus. Presented at: 2025 NANETS Multidisciplinary NET Medical Symposium; October 23-25, 2025; Austin, Texas.
- A trial to assess efficacy and safety of octreotide subcutaneous depot in patients with GEP-NET (SORENTO). Clinicaltrials.gov. Updated November 6, 2025. Accessed November 7, 2025. https://clinicaltrials.gov/study/NCT05050942