TY - JOUR
T1 - 301P Sodium-glucose cotransporter-2 (SGLT-2) inhibitors for alpelisib (ALP)-induced hyperglycemia:
T2 - A report of 6 cases from SOLAR-1
AU - Lu, Y-S.
AU - Chiu, J.
AU - Airoldi, M.
AU - Vila, M. Margeli
AU - Lorenzo, J. Ponce
AU - Ghaznawi, F.
AU - Gaudenzi, F.
AU - Ridolfi, A.
AU - Lorenzo, I.
AU - Borrego, M. Ruiz
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
UR - https://www.mendeley.com/catalogue/600d942e-b679-3de7-a35c-11595ffcfa9b/
U2 - 10.1016/j.annonc.2020.08.403
DO - 10.1016/j.annonc.2020.08.403
M3 - Article
VL - 31
SP - S363-S363
IS - Supl. 4
ER -
