In 2019, PI3K inhibitors became a new treatment option for postmenopausal women and men with HR-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer with the U.S. Food and Drug Administration’s approval of alpelisib in combination with fulvestrant. Although alpelisib remains the only PI3K inhibitor approved today, others are in clinical trials, and the new class of agents has a unique safety profile.
In their article in the December 2020 issue of the Clinical Journal of Oncology Nursing, Donahue and Fulgencio provided an overview of the most common adverse events associated with PI3K inhibitors with implications for oncology nurses to monitor, manage, and educate patients about their occurrence.
Nurses’ Role in PI3K Adverse Events
Most of the common adverse events associated with PI3K inhibitors are reversible and well-managed with preemptive and early care, Donahue and Fulgencio said. However, persistent, progressive, or severe adverse events may require dose reductions, treatment interruption, or permanent discontinuation.
The most frequently reported adverse events during PI3K inhibitor treatment are hyperglycemia, rash, diarrhea, fatigue, and alopecia. Patient education before treatment begins is critical to prepare patients for the possibility of developing the adverse events and to implement preventive strategies for certain events, Donahue and Fulgencio explained. When adverse events occur, reporting them immediately will allow providers to manage them quickly before they escalate and keep patients on therapy.
Donahue and Fulgencio also emphasized the importance of the entire interprofessional team in addressing adverse events from PI3K inhibitors, including patients’ primary care physicians, endocrinologists, and dermatologists. Oncology nurses have a role in facilitating communication among providers and explaining management recommendations to patients.
Management Strategies for PI3K Adverse Events
Hyperglycemia: “Because the PI3K signaling pathway regulates glucose homeostasis, hyperglycemia is regarded as an on-target effect of PI3K inhibition,” Donahue and Fulgencio said. In alpelisib’s clinical trials, approximately 65% of patients experienced hyperglycemia, with most instances developing around 15 days after treatment began.
Test patients’ fasting plasma glucose and glycosylated hemoglobin before initiating treatment and periodically throughout treatment. Fasting blood or plasma glucose testing is recommended at least once per week in the first two weeks followed by at least every four weeks and then as clinically indicated; glycosylated hemoglobin testing is recommended every three months and then as clinically indicated.
Lifestyle management strategies for patients include reducing carbohydrate-rich processed foods, engaging in 30 minutes of moderate aerobic activity per day, and eliminating tobacco products. Oncology clinicians should work closely with patients’ endocrinologists to monitor and manage patients, including the consideration of antihyperglycemia medication (e.g., metformin, insulin sensitizers such as thiazolidinediones or dipeptidyl peptidase-4 inhibitors).
Rash: Like many targeted therapies, PI3K inhibitors are often associated with rash—specifically maculopapular with these agents. About 12%–52% of patients reported rashes during the clinical trials, but the percentage dropped to 27% when patients were given prophylactic antihistimines (e.g., loratadine) and followed good skincare practices (e.g., use mild soaps, nonocclusive emollients, and sunscreen; avoid sun exposure).
Document a thorough skin assessment and dermatologic history before patients begin treatment to ensure accurate grading of any rash-based adverse events. Topical steroids are first-line treatment of any-grade rash, with the addition of oral antibiotics as needed. For grade 2 or higher, oral steroids are added. Consult with dermatology for severe rash or unresolved symptoms.
Pruritis: Patients may have general pruritis in addition to that associated with a rash. Usually developing within the first two months of treatment, it’s characterized by an intense itching sensation on the skin. Management involves the use of antihistamines (e.g., hydroxyzine), and topical and oral corticosteroids, although treatment interruption may be required.
Stomatitis: About 10%–33% of patients developed stomatitis in the drug’s clinical. Prevention and management strategies include good oral hygiene, mouthwashes (e.g., salt and baking soda rinses, magic mouthwash), and dexamethasone oral solution. Add topical steroids (e.g., triamcinolone dental paste) as needed. To prevent or treat herpes simplex virus–related stomatitis, use antiviral medications (e.g., valacyclovir).
Alopecia: Clinical trials have not linked hair loss to PI3K inibitors, but patients may experience the adverse event from previous or concurrent endocrine therapy, Donahue and Fulgencio said. Studies have shown that using hair and nail supplements and collagen peptides, increasing protein intake, and applying topical minoxidil may provide moderate to significant improvement in patients with breast cancer treated with endocrine therapy.
Diarrhea: Approximately 26%–60% of patients developed any-grade diarrhea in the clinical trials, Donahue and Fulgencio reported. Before beginning treatment, oncology nurses should document patients’ history of chronic diarrhea, laxative use, and comorbidities that may contribute to the development or exacerbation of diarrhea. Provide patient education about the potential for diarrhea and when to call their healthcare provider (e.g., four or more stools per day, change in stool characteristics).
Management includes dietary changes and administration of antidiarrheal medication (e.g., diphenoxylate/atropine or loperamide) after the first loose stool and then additionally as needed.
Nausea and vomiting: In the drug’s clinical trials, about 33%–45% of patients experienced nausea and 10%–27% had vomiting, Donahue and Fulgencio said. Ask patients about frequency, duration, and activities that may trigger the adverse event, then implement management strategies tailored to their experience, such as suggesting bland meals high in calories and clear liquids and rest and deep breathing after eating. For more severe events, consider using prophylactic antiemetic regimens (e.g., olanzapine), an as-needed antiemetic (e.g., ondansetron), and IV saline or fluids as required for rehydration.
Other adverse events: Fatigue is a common adverse event for all patients with cancer, and 42% of patients reported it in PI3K inhibitor clinical trials; however, it may stem from other triggers such as tumor biology or comorbidities. Ask patients about their sleep habits, psychosocial well-being, and thyroid function, and consider referring them to sleep clinics or the psychology department.
PI3K inhibition decreased appetite for 16%–36% of the patients in the clinical trials. Ensure patients maintain their caloric intake while reducing carbohydrates to prevent weight loss, and consider referral to a dietician.
Grade 3 or greater laboratory abnormalities that result from PI3K inhibition include increased liver enzymes and decreased potassium, lymphocytes, and hemoglobin, Donahue and Fulgencio said. Nurses should assess for other possible causes (i.e., alcohol and excessive acetaminophen use for increased liver enzymes) and managing possible contributors (i.e., diarrhea and vomiting).
For more information about managing adverse events with PI3K inihibitors, refer to the full article by Donahue and Fulgencio.