301P Sodium-glucose cotransporter-2 (SGLT-2) inhibitors for alpelisib (ALP)-induced hyperglycemia: A report of 6 cases from SOLAR-1

Y-S. Lu, J. Chiu, M. Airoldi, M. Margeli Vila, J. Ponce Lorenzo, F. Ghaznawi, F. Gaudenzi, A. Ridolfi, I. Lorenzo, M. Ruiz Borrego

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: In the phase III SOLAR-1 trial (NCT02437318), ALP (PI3Kα inhibitor) + fulvestrant (FUL) significantly improved progression-free survival vs. FUL alone in patients (pts) with HR+/HER2− advanced breast cancer with PIK3CA mutations. Hyperglycemia was identified as an on-target adverse event of ALP. ADA guidelines recommend concomitant treatment with initial metformin as well as insulin sensitizers and DPP-4 inhibitors. SGLT-2 inhibitors have emerged as hypoglycemic agents, reducing glucose renal reabsorption to facilitate its excretion. Here we present a case report on the use of SGLT-2 inhibitors for the management of ALP-induced hyperglycemia in SOLAR-1. Methods: Hyperglycemia was assessed at baseline and over time using fasting plasma glucose and glycated haemoglobin. Results: In SOLAR-1, 284 pts were randomized to ALP + FUL, median duration of ALP exposure was 5.5 months, and 190 pts (67%) developed hyperglycemia as of 30 Sept 2019, with 18 pts (6%) discontinuing ALP treatment due to hyperglycemia. A total of 166 pts received concomitant hypoglycemic medications, mainly metformin (87%). In addition to metformin, 6 pts received an SGLT-2 inhibitor, consisting of empagliflozin, ipragliflozin, and dapagliflozin. All 6 pts had ≥ 1 risk factor at baseline for developing hyperglycemia: prediabetes (n = 4; 1 with history of type 2 diabetes), diabetes (n = 2), and obesity (n = 2). The most severe hyperglycemia in these pts was grade (G) 3 (n = 5). After initiating an SGLT-2 inhibitor, all subsequent hyperglycemia events were G 1/2, except one G 3 event with steroids as a confounding factor. Duration of ALP ranged from 9.5 to 27.7 months in pts who discontinued; 2 pts were continuing to receive ALP after 37.0 and 40.0 months, respectively. None of the 6 pts discontinued ALP due to hyperglycemia. Conclusions: In 166 pts treated for ALP-related hyperglycemia, 87% received metformin-based concomitant hypoglycemic medications. In 6 pts, addition of an SGLT-2 inhibitor stabilized blood glucose level, allowing them to continue ALP treatment. These results warrant further investigation of using SGLT-2 inhibitors for ALP-induced hyperglycemia in a larger sample size study. 
Original languageEnglish
Pages (from-to)S363-S363
Number of pages1
JournalAnnals of Oncology
Volume31
Issue numberSupl. 4
DOIs
Publication statusPublished - Sept 2020

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