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

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. Clinical trial identification: NCT02437318 (May 7, 2015). Editorial acknowledgement: Medical writing support was provided by Mihaela Marina, PhD, at MediTech Media, Ltd, funded by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study: Novartis Pharmaceuticals Corporation. Funding: Novartis Pharmaceuticals Corporation. Disclosure: Y-S. Lu: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy; Speaker's Bureau: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy: Pfizer; Research grant/Funding (institution), Research Grant: Roche; Research grant/Funding (institution), Research Grant: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Boehringer Ingelheim; Honoraria (self), Speaker Bureau/Expert testimony, Speaker's Bureau: Eisai. M. Margeli Vila: Advisory/Consultancy, Advisory/Consultancy: Novartis; Advisory/Consultancy, Advisory/Consultancy: Pfizer; Advisory/Consultancy, Advisory/Consultancy: Roche; Advisory/Consultancy, Advisory/Consultancy: Kern. F. Ghaznawi: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employment and Stock Ownership: Novartis. F. Gaudenzi: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employment and Stock Ownership: Novartis. A. Ridolfi: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employment and Stock Ownership: Novartis. I. Lorenzo: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employment and Stock Ownership: Novartis. M. Ruiz Borrego: Research grant/Funding (institution), Research Grant: Novartis; Research grant/Funding (institution), Research Grant: Eli Lilly; Research grant/Funding (institution), Research Grant: Pfizer. All other authors have declared no conflicts of interest.