Pancreatic exocrine insufficiency (PEI) in patients (pts) with well-differentiated neuroendocrine tumours (wd-NETs) treated with somatostatin analogues (SSAs): Incidence and impact on quality of life

Background: Advanced wd-NET patients (pts) are commonly treated with SSAs. PEI may be under-estimated in trials due to difficulties in distinguishing carcinoid syndrome-related diarrhoea and PEI.Methods: In this single-institution, prospective, observational study, sequential pts with advanced wd-NET were commenced on SSAs and followed for a minimum of 12 months (or until disease progression). Toxicity was prospectively assessed monthly. Faecal elastase testing (FE) (for diagnosis of PEI) and quality of life (QoL) questionnaires (QLQ-C30 and QLQ-GI.NET21) were performed 3-monthly.Results: Of 52 pts recruited (Jan 15-Apr 16), 50 were eligible: median age 65.8 yrs; 58% male; ECOG performance status 0 (42%), 1 (46%) or 2 (12%); primary: small bowel (60%), pancreas (22%), lung (12%) and other (6%). Baseline median Ki-67 was 3.1% (range 0.7-25), serum 5HIAA: 195 nmol/L (95%CI 145-318) and chromogranin A (CgA): 327 ng/mL (95%CI 140-582). Most pts were metastatic (92%), non-functional (66%) and started SSA first-line (88%); depot SSA was octreotide in 60%, lanreotide in 40%. Forty-one pts (82%) started full-dose SSA (4-weekly octreotide 30mg or lanreotide 120mg); 96% achieved full dose; 3 pts required dose reduction due to toxicities. Grade (G) 1-2 toxicities were flatulence (50%), abdominal pain (32%), diarrhoea (30%), fatigue (20%), PEI (22%), nausea (16%), hyperglycaemia (6%), anorexia (4%) and constipation (2%). G 3-4 toxicities were few (G3 hyperglycaemia (n = 1) and G3 PEI (n = 1); no G4). Twelve pts (24%) developed SSA-related PEI (4 clinical diagnosis, 8 FE-confirmed) at a median of 2.9 mo (95%CI 1.7-8.6) after starting SSA; 11/12 (92%) pts received enzyme replacement. Questionnaires identified fatigue, insomnia and diarrhoea as the most important baseline symptoms; SSA therapy did not negatively-affect QoL. Estimated median progression-free survival (PFS) was 29.9 mo (95%CI 21.4-not reached). High baseline CgA was an independent factor for shorter PFS (HR 1.01 (95%CI 1.001-1.1); p-value 0.001) after adjustment for other factors (baseline 5HIAA, Ki-67).Conclusions: SSA-induced PEI occurs in 1:4 pts; clinicians should actively identify and treat.