High-dose somatostatin analogues (SSAs) can be effective and well-tolerated second-line therapies in neuroendocrine tumours (NETs) progressing on standard-dose SSAs in selected cases, according to Dr Ingrid Mak of the University of Hong Kong, at the 7th Endocrinology, Diabetes & Metabolism Hong Kong Annual Meeting (EDM HK 2024).

Long-acting SSAs (eg, octreotide LAR and lanreotide AG) remain first-line treatment for well-differentiated advanced low-grade (ie, G1 or 2) NETs with Ki-67 <10 percent and low tumour burden. The latest 2024 European Neuroendocrine Tumor Society (ENETS) guidelines recommend expanded use of these agents in high doses in patients with slow-progressing disease (especially small bowel NETs [Si-NET]), low Ki-67 and low tumour burden, to delay the use of more toxic treatment. High-dose SSAs can also be used in patients with comorbidities such as severe renal insufficiency or impaired bone marrow function who cannot tolerate other therapies, such as peptide receptor radionuclide (PRRT), or in whom these or other systemic therapies are contraindicated or not an option. [J Endocrinol Invest 2024;47:35-46; J Neuroendocrinol 2024;36:e13423]

These ENETS recommendations are supported by the CLARINET FORTE trial evaluating the efficacy of lanreotide AG 120 mg Q14D in patients with progressive Si-NET or pancreatic NET (pNET) following first-line standard-dose lanreotide AG treatment (120 mg Q28D), which reported a median progression-free survival (PFS) of 8.3 months in the mid-gut cohort and 5.6 months in the pancreatic cohort. In patients with Ki-67 ≤10 percent, those with mid-gut NET had a median PFS of 8.6 months and a median duration of stable disease (DoSD) of 13.8 months, while those with pNET had median PFS and median DoSD of 8.0 and 8.3 months, respectively. The patients’ quality of life did not deteriorate during the study, and no treatment-related serious adverse events were reported. [Eur J Cancer 2021;157:403-414]

Pasireotide, a second-generation multireceptor-targeted SSA with high affinity for somatostatin receptor subtypes (highest for subtype 5, followed by 2, 3 and 1), is a promising therapy for hormonal control in functional NETs, especially insulinoma and carcinoid syndrome (CS) refractory to other SSAs. It is recommended in the latest ENETS guidelines for octreotide/lanreotide-refractory CS patients without radiological progression.

“SSAs are the only drugs for NETs that endocrinologists can prescribe easily, comfortably and free of charge in a public hospital setting,” noted Mak. “Financial burden is a general concern for patients with NETs in Hong Kong. Since SSAs are effective and well tolerated, we should make good use of available resources according to our drug formulary, as imaging studies [dual tracer PET-CT] and other therapeutic options [PRRT/everolimus] are self-financed and costly [although from a practical standpoint, somatostatin receptor imaging is not mandatory but is generally recommended],” she concluded.