Alpelisib for Long-term Management of Tumor-Induced Hypoglycemia.
Overview
abstract
BACKGROUND/OBJECTIVE: Tumor-induced hypoglycemia (TIH) is a rare and often fatal complication of cancers that produce or induce secretion of hormones such as insulin, insulin-like growth factor 2, and proinsulin. We present a case series describing the effectiveness and tolerability of the phosphatidylinositol 3-kinase inhibitor alpelisib in 2 women with metastatic insulin-producing or proinsulin-producing tumors. CASE PRESENTATION: Over 4 to 8 months of follow-up, it was observed that alpelisib resulted in reductions in hypoglycemic rates (<54 mg/dL) as assessed on continuous glucose monitoring. For the first patient, the proportion of glucose readings <54 mg/dL fell from 2.3% (95% CI, 2.1-2.4) to 0.2% (95% CI, 0.2%-0.3%), and the rate ratio was 0.087 (95% CI, 0.086-0.089). For the second patient, the proportion of low glucose readings fell from 9.0% (95% CI, 8.6-9.4) to 2.0% (95% CI, 2.2%-2.5%), and the rate ratio was 0.26 (95% CI, 0.26-0.27). Alpelisib was not associated with significant adverse events. There was one instance of gastrointestinal bleeding that was likely not attributable to alpelisib. Due to high cost and off-label use, the process of obtaining alpelisib was complex and took several months for the first patient and 2 years for the second patient. DISCUSSION: Treatment options for TIH are limited. Alpelisib, a small-molecule phosphatidylinositol 3-kinase inhibitor, may blunt the hypoglycemic effect of excess insulin and proinsulin by decreasing glucose transport and increasing glycogenolysis and gluconeogenesis. CONCLUSION: Alpelisib appears to be effective and well tolerated for long-term treatment of TIH.
