253P Risk factor (RF) identification (ID) and hyperglycemia (HG) prevention with alpelisib (ALP) + fulvestrant (FLV) in PIK3CA-mutated, hormone-receptor positive (HR+), human epidermal growth factor-2 negative (HER2-) advanced breast cancer (ABC)

Abstract

Background: A systematic literature review was conducted to summarize first-line (1L) treatments and clinical outcomes among patients with hormone receptor-positive (HR+), human epidermal growth factor 2-positive (HER2+) advanced or metastatic breast cancer (aBC).Methods: Clinical trials and real-world studies (RWS) published between 01/2000-12/ 2020 evaluating clinical outcomes of 1L treatments in adults with HR+/HER2+ aBC were identified through pre-specified searches in Medline, Embase, Cochrane Library, and key conference proceedings. Study and patient characteristics, treatments (anti-HER2 therapy [AHT]+chemotherapy [CT], AHT+endocrine therapy [ET], ET only, and AHT only), treatment strategy (no induction vs. induction and maintenance), and outcomes (e.g., progression-free survival [PFS], overall survival [OS]) were extracted and summarized.Results: Overall, 20 trials and 21 RWS were identified. Among trials, treatments with AHT+CT (70%), AHT+ET (17%), ET only (10%), and AHT only (3%) were evaluated across 30 study arms. Fourteen of these study arms included induction and maintenance treatments, of which induction with AHT+CT (79%), CT only (14%), and AHT only (7%) were evaluated. Median PFS and OS ranged from 2.4-23.7 months and 23.9-66.7 months, respectively, in trials. Among RWS, AHT-based regimens (71%), ET alone (10%), CT alone (5%), or a combination (15%) were evaluated across 41 study arms. Eleven (27%) and 3 (7%) study arms assessed treatments in the induction and maintenance setting and with no induction therapy, respectively, while 27 (66%) could not be evaluated. Induction regimens used included AHT+CT (82%), AHT only (9%), and ET only (9%). Real-world median PFS and OS ranged from 4.8-29.0 months and 26.0-80.4 months, respectively. All studies measured PFS/OS from any 1L treatment initiation for aBC or earlier.Conclusions: There is considerable variation in treatments and clinical outcomes in this patient population. Though most real-world patients with HR+/HER2+ aBC receive AHT-based regimens in the 1L setting, few also receive ET.

The efficacy and safety of alpelisib in breast cancer: A real-world analysis

“…8 The authors found that the implementation of this protocol led to a reduction in grade 3-4 hyperglycemia events. 8 Lastly, a multicenter, phase II trial is ongoing to determine if metformin prophylaxis is effective in preventing hyperglycemia events with alpelisib in all patients regardless of risk factors. 9…”

“…8 The authors found that the implementation of this protocol led to a reduction in grade 3-4 hyperglycemia events. 8 Lastly, a multicenter, phase II trial is ongoing to determine if metformin prophylaxis is effective in preventing hyperglycemia events with alpelisib in all patients regardless of risk factors. 9 Although the BYLieve trial gives insight into alpelisib + fulvestrant after a CDK4/6i, alpelisib + fulvestrant is commonly used as a salvage agent in the real-world setting due to prolonged efficacy of other first-line therapies and concerns of high rates of adverse effects.…”

“…8 These medications were initiated for patients based on clinical risk factors, such as age ≥ 65, BMI ≥ 25 kg/m2, baseline fasting plasma glucose ≥ 100 mg/dL, and A1c ≥ 5.7%. 8 The authors found that the implementation of this protocol led to a reduction in grade 3-4 hyperglycemia events. 8 Lastly, a multicenter, phase II trial is ongoing to determine if metformin prophylaxis is effective in preventing hyperglycemia events with alpelisib in all patients regardless of risk factors.…”

“…While there are new guidelines suggesting starting metformin pre-emptively in high-risk patients, the current data is limited to a single-center, retrospective study. 7,8 This study implemented a preventative protocol for 16 women utilizing metformin, a thiazolidinodione, or a DPP-4 inhibitor to minimize the incidence of hyperglycemia, dose reductions, and drug discontinuation of alpelisib + fulvestrant. 8 These medications were initiated for patients based on clinical risk factors, such as age ≥ 65, BMI ≥ 25 kg/m2, baseline fasting plasma glucose ≥ 100 mg/dL, and A1c ≥ 5.7%.…”

Management Strategies for Hyperglycemia Associated with the α-Selective PI3K Inhibitor Alpelisib for the Treatment of Breast Cancer

“…Given the early onset and frequency of hyperglycemia associated with alpelisib, a pre-emptive approach to management is recommended. Although there is currently only limited evidence supporting this practice [ 44 ], metformin along with lifestyle changes can be considered for the prevention of alpelisib-induced hyperglycemia in prediabetic patients or high-risk patients with normal baseline glycemic status. According to a recent review by Anders et al, many oncologists initiate 500 mg of metformin extended release (XR) 7 days before starting alpelisib in high-risk patients [ 24 ].…”