Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Hyperglycaemia secondary to phosphatidylinositol-3 kinase (PI3K) inhibition (#627)

Arunan Sriravindrarajah 1 2 , Joshua Hurwitz 1 2 3 4 , Elgene Lim 1 2 3 4 , Jerry R Greenfield 1 2 3
  1. St Vincent’s Hospital, Sydney, NSW, Australia
  2. School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia
  3. Garvan Institute of Medical Research, Sydney, Australia
  4. Kinghorn Cancer Centre, Sydney, NSW, Australia

Phosphatidylinositol-3 kinase (PI3K) is a critical intracellular pathway regulating cell growth and survival [1]. Hyperactivation of the PI3K pathway is associated with almost all human cancers, and PI3K inhibition has been proposed as a treatment option for selected cancers [1]. However, PI3K is a important mediator of the action of insulin and PI3K inhibitors have been associated with hyperinsulinaemic hyperglycaemia [2].

A 63-year-old Pacific Islander female was referred for Grade 3 hyperglycaemia (blood glucose level [BGL] 24.4mmol/L) following two weeks treatment with inavolisib 9mg daily, a trial drug inhibiting the PI3K catalytic subunit alpha, and fulvestrant for metastatic breast cancer. She had no personal or family history of diabetes mellitus or recent glucocorticoid usage. Body mass index was 29.1 kg/m2 and investigations prior to commencing inavolisib demonstrated HbA1C 5.3% and fasting BGL 4.8 mmol/L. CT Abdomen Pelvis did not identify any pancreatic lesions.

She was treated with metformin 500mg BD and Optisulin 10 units daily but remained hyperglycaemic. She self-ceased inavolisib and Optisulin following which fasting BGL normalised to 5.9mmol/L within 72 hours. Upon recommencement of inavolisib, fasting BGLs increased to 7-9mmol/L and pre-dinner BGLs increased to 13-21mmol/L. She was advised to reduce carbohydrate intake and recommence Optisulin 10 units daily, but continued to experience Grade 3 hyperglycaemia. A 33% dose reduction to inavolisib 6mg daily was implemented per the clinical trial protocol. The patient themselves made a further dose reduction to inavolisib 3mg daily. Following the dose reduction, glycaemic control normalised with BGLs consistently <8 mmol/L on metformin alone. However, the patient had progression of her liver metastases on imaging 2 months later, and inavolisib was ceased as per the trial protocol.

This case demonstrates the potent hyperglycaemic effect of PI3K inhibition in patient without a history of diabetes mellitus. All patients treated with PI3K inhibitors should monitor BGL.

  1. Yang J, Nie J, Ma X, Wei Y, Peng Y, Wei X. Targeting PI3K in cancer: mechanisms and advances in clinical trials. Molecular Cancer. 2019;18(1):26
  2. Tankova T, Senkus E, Beloyartseva M, Borštnar S, Catrinoiu D, Frolova M, et al. Management Strategies for Hyperglycemia Associated with the α-Selective PI3K Inhibitor Alpelisib for the Treatment of Breast Cancer. Cancers (Basel). 2022;14(7):1598.