Alpelisib for Long-term Management of Tumor-Induced Hypoglycemia.

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.