Clinical impact of unsuccessful subcutaneous administration of octreotide LAR instead of intramuscular administration in patients with metastatic gastroenteropancreatic neuroendocrine tumors

Octreotide LAR is a long-acting somatostatin analogue (SSA) used in the management of metastatic gastroenteropancreatic neuroendocrine tumors (GEP NETs). It requires intramuscular (IM) injection. Missed IM injections cause subcutaneous nodules (SCNs) on radiologic images. We reviewed the rates of SCNs in a real-world cohort of GEP NETs receiving octreotide LAR and explored treatment outcomes. Patients commencing octreotide LAR between August 5, 2010 and March 8, 2018 at a single cancer center in Canada were identified from pharmacy records. Patients were included if they had a computed tomography (CT) scan performed at the time of progression and a preceding CT with pelvis included to enable assessment for the presence of nodules. Fisher's exact test was used to examine predictors of SCNs, and Kaplan-Meier curves summarized differences in progression free (PFS) and overall survival (OS) that were compared with log-rank tests. Of 243 patients receiving octreotide LAR, 45 had all required CT images available for central review. SCNs were found in 20/45 (44%) of patients on the last scan showing stable disease before progression and were numerically but not statistically more likely in females (OR: 2.36, 95% CI: 0.66-8.29, p = .23). There was an increased risk of SCNs in patients with a skin-to-muscle distance >38 mm (the length of an octreotide LAR needle) on CT (OR: 5.09, 95% CI: 1.39-16.6, p = .018) and a trend toward increased risk in obese patients (OR: 5.71, 95% CI: 1.26-23.4, p = .061). PFS (HR: 1.01, 95% CI: 0.56-1.78, p = .98) and OS (HR: 0.86, 95% CI: 0.41-1.8, p = .70) was similar between those with/without SCNs. In conclusion, almost half of patients receiving octreotide LAR had SCNs; however, missed administration of SSA did not appear to result in worse survival in this small study. Factors such as sex, younger age skin-to-muscle distance, and obesity may affect SCN development and should be considered when choosing an SSA.