Background: PIK3CA, the gene encoding the α-subunit of phosphatidylinositol-3-kinase (PI3Kα), is mutated in ~40% of hormone receptor–positive (HR+), HER2– advanced breast cancer (ABC) tumors. These mutations can drive malignant transformation and are a negative prognostic factor in these patients. Alpelisib, an α-selective PI3K inhibitor and degrader, plus fulvestrant is approved for PIK3CA-mutated, HR+, HER2– ABC based on the phase 3 SOLAR-1 trial (NCT02437318). For patients with PIK3CA-mutated disease, alpelisib plus fulvestrant compared with placebo plus fulvestrant improved progression-free survival (hazard ratio, 0.65, median 11.0 months vs 5.7 months) and had a tolerable safety profile. Hyperglycemia and rash, which are considered on-target effects of PI3K inhibitors, were frequently observed.
Objective: To provide an oncology nurse’s perspective on recent SOLAR-1 findings that may affect the care of alpelisib-treated patients. The rationale is that more detailed adverse event (AE) management guidelines have been shown to improve alpelisib safety outcomes.1
Methods: A qualitative analysis of SOLAR-1 data of potential interest to oncology nurses presented at congresses between July 1, 2020, and July 10, 2021, was performed.
Results: Overall, PI3K inhibitor–associated hyperglycemia management continues to be a highly active area of investigation. In a recent ad hoc analysis, a risk factor model identified baseline fasting plasma glucose, body mass index (BMI), glycosylated hemoglobin, monocyte count, and age as top predictors for developing grade 3/4 hyperglycemia.2 When applied to SOLAR-1, this model showed that ~90% of the 106 patients classified as “high risk” developed grade 3/4 hyperglycemia (vs 7% of the 178 low-risk patients). Notably, most (86%) high-risk patients remained on alpelisib treatment. Another study showed that 6 SOLAR-1 patients who received sodium-glucose cotransporter-2 inhibitors with other antihyperglycemia agents were able to stay on alpelisib treatment despite having ≥1 baseline risk factors for this AE (prediabetic/diabetic status, BMI ≥30, or age ≥75 years) and had longer duration of alpelisib treatment versus all patients.3 Another analysis showed that, for patients with grade 1/2 hyperglycemia, delayed intervention with antihyperglycemia medication (44 patients) resulted in a higher chance of hyperglycemia not improving or worsening versus early intervention (22 patients).4 Finally, an analysis of long-term disease control (progression-free survival ≥18 months, which was achieved by 30% of alpelisib-treated patients) showed that diabetes/prediabetes at baseline, as well as poor prognosis and heavy pretreatment, do not preclude long-term benefit from this combination.5
Conclusions: From the nursing perspective, results from these studies reinforce our observations that alpelisib-associated hyperglycemia can be effectively managed with early detection and intervention. Notably, this also appears to be true for patients with baseline risk factors such as high blood glucose and high BMI. Ultimately, the goal of AE management is to keep patients on therapy for as long as possible to help delay disease progression. In our experience, patient education before alpelisib initiation and follow-up is also critical for optimal control and prevention of hyperglycemia. Further studies are needed on potential barriers to monitoring and managing hyperglycemia, such as insurance coverage for proactive use of medication and at-home monitoring devices.
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