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.
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.
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).
SSA-induced PEI occurs in 1:4 pts; clinicians should actively identify and treat.
Clinical trial identification
Legal entity responsible for the study
Dr. Lamarca was part-funded by the European Society for Medical Oncology Translational Fellowship Programme and by the Spanish Society of Medical Oncology (SEOM) Fellowship Programme. Dr Barriuso was funded by the Spanish Society of Medical Oncology (SEOM) Fellowship Programme.
All authors have declared no conflicts of interest.