Characterization of inavolisib-associated hyperglycemia in metastatic hormone receptor–positive (HR+) breast cancer.

Abstract

e13055 Background: Inavolisib + palbociclib + fulvestrant is approved in patients with HR+, HER2-, PIK3CA -mutant MBC based on INAVO120, which demonstrated significant progression-free survival and overall survival benefit in the first line compared with palbociclib + fulvestrant. In INAVO120, 63.4% of patients developed any-grade hyperglycemia (HG) and 6.8% developed grade 3-4 HG despite eligibility requirement of fasting glucose ≤126mg/dl and hemoglobin A1c (HbA1c) ≤6%. Here we describe the incidence and treatment of inavolisib-associated HG in a single center cohort. Methods: Patients with MBC who received inavolisib as standard care from 10/2024–1/2026 at Memorial Sloan Kettering Cancer Center and had ≥1 on-treatment glucose were included in this retrospective study. Patient and tumor characteristics, pretreatment body mass index (BMI), HbA1c, on-treatment glucose levels, and details on HG management were abstracted. HG was graded per CTCAE v4.0. Results: 40 female patients were included in this study. Median age was 65 (range 39-92). 21 patients (53%) received inavolisib in the first-line setting and 11 (28%) received it in the second-line (range 1-11 th line). Median pretreatment BMI was 26.2 kg/m 2 (range 20.3-47.0). Among 31 (78%) patients with pretreatment HbA1c levels available, median HbA1c was 5.5% (range 4.7-6.9%); 17 (55%) had normal HbA1c, 10 (32%) had HbA1c in the prediabetes range (5.7-6.4%), and 4 (12.9%) had HbA1c in the diabetes range (≥6.5%). 23 patients (58%) developed HG of any grade; 4 (10%) developed grade 1, 10 (25%) developed grade 2, and 9 (23%) developed grade 3 HG. The median time to onset of any-grade HG was 42 days (range 4-226). Among those who developed HG, 11 (48%) received anti-hyperglycemic medications; 7 patients received 1 or 2 anti-hyperglycemic agents whereas 4 patients required ≥3 anti-hyperglycemic agents. In 10/11, metformin was the first anti-hyperglycemic initiated and in 7, an SGLT2 inhibitor was the next anti-hyperglycemic initiated. 4 patients were treated with insulin, 1 of whom had HbA1c in the prediabetes range and 2 of whom had HbA1c in the diabetes range before inavolisib. 12 patients were referred to endocrinology. Among the total cohort, inavolisib was held until resolution of HG in 10 patients (25%) and dose-reduced due to HG in 7 patients (18%). 4 patients (10%) discontinued inavolisib due to HG; 3 of these patients required insulin, 2 had prior inavolisib dose reductions, 1 had pretreatment HbA1c in the diabetes range and 2 had HbA1c in the prediabetes range. Conclusions: Real-world rates of HG with inavolisib in this single-center cohort underscore the importance of baseline metabolic assessment, proactive glucose monitoring, and management to minimize inavolisib interruptions. As a limitation, fasting status was not uniformly documented so some glucose values may have been non-fasting, affecting HG grading.