Faculty Bibliography

PURPOSE:Patients with epidermal growth factor receptor (EGFR) mutation-positive (EGFRm) non-small-cell lung cancer commonly experience disease progression in the CNS. Here, we assess the impact of CNS disease on resource utilization and outcomes in patients who are EGFRm. METHODS:We completed a retrospective review of all advanced patients who were EGFRm, referred to BC Cancer, and treated with a first- and/or second-generation EGFR tyrosine kinase inhibitor from 2010 to 2015. Baseline characteristics, systemic treatment, and CNS management were collected. We compared health resource utilization (HRU) between patients with CNS-negative disease and those with CNS metastases from the median time of CNS metastases diagnosis to death or last follow-up (9.1 months) and at 9 months preceding death or last follow-up for the CNS-negative group. RESULTS:Four hundred ninety-nine patients were referred, of which 68% were female; 51% were of Asian ethnicity; and 57%, 37%, and 6% were exon 19, 21, or other, respectively; with a median age of 66 years. Two hundred twenty-nine (46%) of 499 patients developed CNS metastases-39% at diagnosis and 61% over the course of disease. CNS metastases were managed with surgery with or without whole-brain radiotherapy (WBRT; 13%) WBRT alone (73%), stereotactic radiosurgery with or without WBRT (5%), or no CNS-directed therapy (9%). The median time from the development of CNS metastases diagnosis to death was 9.1 months. CNS-negative patients used less HRU versus patients that were CNS-positive in the 9 months preceding death or last follow-up-in the average number of clinic visits (8.53 v 12.71, respectively; P < .001), hospitalizations (0.43 v 0.76, respectively; P < .001), CNS imaging investigations (0.52 v 2.65, respectively; P < .001), emergency room visits (0.03 v 0.14, respectively; P = .001), palliative care unit admission (8% v 10%, respectively; P = .64), and hospice admission (3% v 19%, respectively; P < .001). CONCLUSION:The incidence of CNS metastases in patients with EGFRm is high and associated with increased HRU. Prevention or delay of CNS metastases with newer systemic therapy options may translate into lower resource utilization.

Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) represent a heterogeneous group of tumors that is associated with an indolent course. Octreotide has a positive effect on disease stabilization in well-differentiated midgut NETs, but a meaningful survival analysis was not possible due to insufficient events. Higher doses of octreotide long-acting release (LAR) are often used in clinical practice for control of carcinoid symptoms and our objective was to determine if dose of octreotide correlates with survival. We reviewed all patients with advanced GEP NETs who initiated treatment with octreotide LAR between 2000 and 2013 in a large, representative Canadian province. We compared overall survival in patients who received low (< 30 mg) compared to high (≥ 30 mg) doses of octreotide. A total of 170 patients were identified. Baseline characteristics in the low- and high-dose groups were similar: median age 62/63 years, 50/58% were male, 46/48% originated from the small bowel, and 74/66% had liver metastases at diagnosis. The median time from diagnosis to treatment initiation was 5.5 and 6.0 months. Octreotide LAR was initiated with the intent of symptom management (71%), disease stabilization (23%), or biomarker control (6%). Median overall survival (OS) was better in the high-dose group, 66 months compared to 22 months (multivariate HR 0.5, p < 0.01). Age ≥ 65 (HR 1.9, p < 0.01), ECOG ≥ 2 (HR 2.7, p < 0.01), and pancreatic NETs (HR 1.7, p = 0.03) were all predictors of worse survival. Our findings suggest that octreotide may confer survival benefits in GEP NETs. Further prospective studies are warranted to validate the impact of high-dose octreotide on outcomes.