Monitoring and Managing Adverse Events with Capivasertib: Practical Steps for US Oncology Teams
Keywords
Indication and Usage
Capivasertib (TRUQAP®) in combination with fulvestrant is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alteration as detected by an FDA-approved test following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.
Expert opinions are shared in this program and may differ from the approved capivasertib (TRUQAP®) labeling. Please see full Prescribing Information, including Patient Information when making treatment decisions.
INTRODUCTION
Capivasertib is an AKT inhibitor approved in the US. It is used in combination with fulvestrant for adults with HR+/HER2- advanced or metastatic breast cancer with ≥1 PIK3CA, AKT1, or PTEN alteration after prior endocrine therapy in the metastatic setting or within 12 months of adjuvant therapy.1-4
Despite its improved efficacy compared to fulvestrant only,1 capivasertib is associated with three common AEs: diarrhea, rash, and hyperglycemia.
Manage common AEs by informing and preparing your patients, and following a systematic approach to monitoring and management. This graphic will show you how, with three management algorithms based on 10 structured recommendations, detailed in Iyengar et al.,5 to complement the prescribing information.
WHICH AE ARE YOU MANAGING TODAY?
MANAGING DIARRHEA ON CAPIVASERTIB
Inform and prepare patients before their first dose of capivasertib
INFORM
Recommendation 1:
“Educate patients to recognize low-grade diarrhea vs symptoms that require enhanced supportive care.”5
Inform patients that diarrhea is a common treatment-related effect, with a median time to onset of 8 days (range: 2–22 days).5
Prescribe anti-diarrheal treatment and advise patient to have it available before starting capivasertib.5
Instruct patients to notify the healthcare team if they experience ≥4 loose stools above their baseline number of stools per day (Grade ≥2 diarrhea).5
Communicate to patients that the following symptoms may require immediate medical attention:
Fever
(≥100.5 F/38 °C)
Severe abdominal cramping
Signs of dehydration5,7
INFORM AND PREPARE
Recommendation 2:
“Screen for risk factors and use a stool diary.”5
Discuss the importance of your patients keeping a food and stool diary.5
Screen for a history of diarrhea, concomitant medications, and comorbidities that may increase or worsen diarrhea.5 Assess renal function and electrolytes at baseline and identify patients who might be at higher risk of developing dehydration.5,10
USE A STEP-WISE APPROACH TO MANAGEMENT
Recommendation 3:
“Manage diarrhea with a step-wise approach, including dietary counseling, antidiarrheal agents escalated as necessary, and capivasertib dose modifications.”5
Monitor use of loperamide:5
If diarrhea persists beyond 24h despite maximal loperamide, consider additional agents such as diphenoxylate/atropine or octreotide.
Taper antidiarrheals following a 12h diarrhea-free interval.
Counsel patients on dietary modifications:5
Promote regular hydration.
Advise patients to take capivasertib with food.
Advise avoidance or limitation of aggravating foods, including high-fiber foods, lactose, caffeine, and alcohol.
FOCUS ON GRADE-BASED ACTION, REINTRODUCTION, AND PREVENTION OF RECURRENCE
For Grade 2 or 3 diarrhea, withhold capivasertib until recovery to Grade ≤1.5
Increase of <4 stools per day or mild increase in ostomy output
Increase of 4–6 stools per day or moderate increase in ostomy output or limiting instrumental ADL
Increase of ≥7 stools per day or severe increase in ostomy output or limiting self-care ADL or hospitalization indicated
Life-threatening consequences or urgent interventions needed
Maintain same dose
Permanently discontinue
Withhold dose until Grade ≤1
Loperamide dosing schedule differs by grade:
Grade 1 and 2:5
Initiation:
Loperamide 4 mg followed by 2 mg every 4 hours (maximum, 16 mg/day)
Persistent (>24 hours):
Increase loperamide dose, up to 2 mg every 2 hours (maximum, 16 mg/day) and consider alternative anti-diarrheal treatments.
EXPERT INSIGHTS
MANAGING RASH ON CAPIVASERTIB
Inform and prepare patients before their first dose of capivasertib
INFORM AND PREPARE
Recommendation 4:
“Educate patients to recognize capivasertib-associated rash and other symptoms that require enhanced supportive care.”5
Inform patients that skin reactions, including rash, commonly occur with capivasertib, typically around 12 days after starting treatment (range: 10–15 days).5
Advise patients to seek urgent medical care for swelling, chest pain, breathlessness, fever, chills, rapidly worsening rash, blistering, skin peeling, or signs of infection.11
INFORM AND PREPARE
Recommendation 5:
“Implement rash prophylaxis with skin protective measures and a non-sedating H1 antihistamine.”5
Recommend minimizing heat and sun exposure, avoiding skin irritants, using gentle fragrance-free cleansers, and applying emollients regularly.8
Ask patients to report any rash promptly and, where feasible, to photograph it and upload images to the electronic medical record or patient portal.5
Initiate prophylactic treatment with non-sedating H1 antihistamines on Day 1 and continue for the first 8 weeks.5,7,8
USE A STEP-WISE APPROACH TO MANAGEMENT
Recommendation 6:
“Estimate BSA involved by rash to select interventions, including antihistamines, topical or systemic steroids, and capivasertib dose modifications.”5
Conduct a visual inspection of rash characteristics (color, moisture, morphology, and distribution).5,8
Estimate BSA involved using tools like the
palm method:
One palm, including fingers, equals 1% BSA.14,15
Initiate or escalate antihistamines and consider H2 receptor antagonists, topical corticosteroids, and oral/systemic steroids if symptoms persist or are severe.5
When utilizing oral steroids, consider that these can implicate hyperglycemia risk and that glucose monitoring should be intensified.5
FOCUS ON GRADE-BASED ACTION, REINTRODUCTION, AND PREVENTION OF RECURRENCE
For Grade 2 or 3 rash, withhold capivasertib until recovery to Grade ≤1.5
At onset
Macules/papules covering <10% BSA with or without symptoms (e.g., pruritus, burning, tightness)
Macules/papules covering 10–30% BSA with or without symptoms or limiting instrumental ADL or rash covering >30% BSA with or without mild symptoms
Macules/papules covering >30% BSA with moderate or severe symptoms or limiting self-care ADL
Severe bullous, blistering, or exfoliating skin conditions or any % BSA associated with extensive superinfection, with IV antibiotics indicated, or life-threatening consequences
Maintain same dose
Permanently discontinue
*Grading is for maculopapular rash. Refer to Common Terminology Criteria for Adverse Events v5.0 for grading other dermatologic adverse events.
EXPERT INSIGHTS
MANAGING HYPERGLYCEMIA ON CAPIVASERTIB
Be proactive, and inform and prepare patients before their first dose of capivasertib
PROACTIVE CONTROL
Recommendation 7:
“Identify candidates for capivasertib treatment during first-line metastatic breast cancer treatment or earlier to optimize glycemic status.”5
Early monitoring and management of FG during first-line therapy can support a smooth transition to capivasertib with stable glycemic control and may facilitate treatment persistence.5
INFORM
Recommendation 8:
“Screen for hyperglycemia risk factors and provide glucose monitoring education that aligns with the clinic team’s workflows for alerts, triage, and management.”5
Educate patients that capivasertib can cause hyperglycemia, typically emerging at a median of 15 days after initiation (range: 1–51 days), and review common signs and symptoms.5
Consider risk factors for hyperglycemia: BMI ≥30 kg/m², history of prediabetes or diabetes, and use of concomitant medications that increase FG, including systemic corticosteroids, or conditions such as systemic infection and dehydration.5,13,16
PREPARE
Recommendation 9:
“Implement dietary modifications and physical activity prior to and during capivasertib treatment.”5
Encourage a low-carbohydrate, high-fiber diet, regular physical activity, avoidance of substantial weight gain, and limitation of alcohol intake.5
MANAGING HYPERGLYCEMIA IN HIGH-RISK INDIVIDUALS
Recommendation 10:
“Consider hyperglycemia prophylaxis with metformin for patients at elevated risk (i.e., HbA1c ≥5.7%, prediabetes, BMI ≥30 kg/m2, elevated baseline FG); start metformin or escalate existing dose and add other agents to treat hyperglycemia, as needed, while avoiding insulin secretagogues, which can cause hypoglycemia.”5
Support home FG monitoring by providing supplies (glucometer, lancets, test strips) and brief training on morning pre-dose testing.5
Provide a simple calendar and clear instructions to report FG ≥160 mg/dL to the clinic.5
After starting capivasertib, check FG pre-dose on Day 3 or 4 during Weeks 1, 2, 4, 6, and 8, then monthly.5
For high-risk patients (HbA1c ≥5.7%, prediabetes, BMI ≥30 kg/m2, or elevated baseline FG), consider starting extended-release metformin 1 week before capivasertib.5
Capivasertib prescribing information recommends FG evaluation and monitoring.
FOCUS ON GRADE-BASED ACTION, REINTRODUCTION, AND PREVENTION OF RECURRENCE
For Grade 2 or 3 hyperglycemia, withhold capivasertib until recovery to Grade ≤1.5
Maintain same dose
Withhold dose until Grade ≤1
Permanently discontinue
If FG remains elevated despite metformin, consider adding second-line agents and seek endocrinology input.5
Additional HCP intervention:
Consider other complications of hyperglycemia, including diabetic ketoacidosis (DKA), and evaluate serum bicarbonate, electrolytes, ketones, anion gap, and white blood cell count as clinically appropriate.5
EXPERT INSIGHTS
CONCLUSION:
To optimize the benefit from capivasertib, a proactive, team-based strategy is essential. This includes upfront patient education, targeted prophylaxis for rash and hyperglycemia, systematic risk assessment and monitoring, and timely supportive care. Structured, practical AE management can improve patient experience while maintaining treatment efficacy.5
KEY TAKE-HOMES5
Diarrhea
Rash
Hyperglycemia
Identify high-risk patients up front and encourage patients to monitor FG at home if they can or consider in-clinic or local testing facilities.
Consider prophylactic extended-release metformin in higher-risk patients.
Monitor FG according to the recommended schedule.
Begin prophylactic non-sedating antihistamine before treatment.
Encourage immediate reporting of rash with photos.
Advise patients to seek urgent medical care for swelling, chest pain, breathlessness, fever, chills, rapidly worsening rash, blistering, skin peeling, or signs of infection.
Counsel patients to take capivasertib with food, as this may reduce the incidence of diarrhea
Prescribe anti-diarrheal treatment and advise patients to have loperamide on hand before starting capivasertib.
Discuss the importance of your patients keeping a food and stool diary.
Instruct patients to take anti-diarrheal treatment at the first sign of diarrhea.
Instruct patients to notify the healthcare team if they experience ≥4 loose stools above their baseline number of stools per day.
Select Safety Information About capivasertib (TRUQAP®) tablets
TRUQAP is contraindicated in patients with severe hypersensitivity to TRUQAP or any of its components.
Please see full Prescribing Information, including Patient Information for TRUQAP.
Serious adverse reactions include hyperglycemia, including diabetic ketoacidosis and fatal outcomes; diarrhea; and cutaneous adverse reactions. Monitor fasting glucose and hemoglobin A1C levels regularly. May cause fetal harm when administered to a pregnant woman. Among the 355 patients who received TRUQAP in CAPItello-291, the most common (≥20%) adverse reactions, including laboratory abnormalities, were diarrhea (72%), cutaneous adverse reactions (58%), increased random glucose (57%), decreased lymphocytes (47%), decreased hemoglobin (45%), increased fasting glucose (37%), nausea and fatigue (35% each), decreased leukocytes (32%), increased triglycerides (27%), decreased neutrophils (23%), increased creatinine (22%), vomiting (21%), and stomatitis (20%).
References
In the Phase III CAPItello-291 trial, capivasertib with fulvestrant (n=155) significantly improved progression-free survival compared to fulvestrant only (n=134; 7.3 months vs 3.1 months; hazard ratio: 0.50; p<0.001).1
Efficacy data
Safety data
In the Phase III CAPItello-291 trial, the most frequently reported AEs of Grade ≥3 were rash (12.1%), diarrhea (9.3%), and hyperglycemia (2.3%).6,7
Keywords: Adverse events, AKT inhibitor, breast cancer, capivasertib, diarrhea management, dose modification, fulvestrant, hyperglycemia management, MDT care, patient counseling, PI3K pathway, prophylaxis, rash management, toxicity monitoring.
Grade 3 and 4:5
Initiation:
Loperamide 4 mg followed by 2 mg every 2 hours (maximum, 16 mg/day)
Consider alternative anti-diarrheal treatments
If restarting capivasertib, consider scheduled loperamide to prevent recurrence.5
Patients should be encouraged to monitor FG at home if they can or consider in-clinic or local testing facilities.5
Additional Resources
AMJ Podcast | Episode 4: Capivasertib in the Clinic: Strategies to Manage Adverse Events
A Visual Journey into AKT Inhibition
Iyengar NM et al. Optimizing clinical monitoring and management guidelines for capivasertib in HR-positive/HER2-negative advanced breast cancer: expert opinion. npj Breast Cancer. 2026;12(1)16.
References
TRUQAP® (capivasertib) tablets, for oral use. Package insert (Wilmington, DE: AstraZeneca Pharmaceuticals LP, 2025). Available at: https://drd9vrdh9yh09.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/841065f2-fcba-4795-b92a-3afc2ba47325/841065f2-fcba-4795-b92a-3afc2ba47325_pi_med_guide_rendition__c.pdf. Last accessed 11 March 2026.
Burstein HJ et al. J Clin Oncol. 2024;42(12):1450-53.
European Society for Medical Oncology (ESMO). Available at: https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-for-solid-tumours/esmo-mcbs-scorecards?scorecard=409. Last accessed: 12 February 2026.
TRUQAP® (capivasertib) tablets, for oral use. Highlights of Prescribing Information. Available at: https://drd9vrdh9yh09.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/841065f2-fcba-4795-b92a-3afc2ba47325/841065f2-fcba-4795-b92a-3afc2ba47325_viewable_rendition__v.pdf. Last Accessed: 26 February 2026.
Iyengar NM et al. NPJ Breast Cancer. 2025;12(1):16.
Turner NC et al. N Engl J Med. 2023;388(22):2058-70.
Rugo HS et al. ESMO Open. 2024;9(9):103697.
Donahue S, Santos Fulgencio G. Clin J Oncol Nurs. 2020;24(6):673-80.
André F et al. N Engl J Med. 2019;380(20):1929-40.
Maroun JA et al. Curr Oncol. 2007;14(1):13-20.
ChemoCare. Available at: https://chemocare.com/sideeffect/rash. Last accessed: 12 February 2026.
Rugo HS et al. Ann Oncol. 2020;31(8):1001-10.
Gallagher EJ et al. NPJ Breast Cancer. 2024;10(1):12.
Nicolescu AC et al. Life (Basel). 2022;12(12):2050.
Rhodes J et al. Br J Dermatol. 2013;169(1):76-84.
American Diabetes Association Professional Practice Committee. Diabetes Care. 2022;45(Suppl 1):S17-38.
Abbreviations
AE: adverse event; AKT: Ak strain transforming; BSA: body surface area; FG: fasting glucose; H1: histamine H1 receptor; H2: histamine H2 receptor; HER2: human epidermal growth factor receptor 2; HR: hormone receptor; IV: intravenous; PI3K: phosphatidylinositol 3-kinase; PTEN: phosphatase and tensin homolog; vs: versus.
Withhold dose until Grade ≤1
Counsel patients to take capivasertib with food, as this may reduce the incidence of diarrhea.5