How Do AKT Inhibitors Work?

AKT inhibitors are a novel class of medications in the treatment of certain types of locally advanced or metastatic breast cancers with specific gene mutations as confirmed by an FDA-approved test. AKT inhibitors are approved for use in combination with fulvestrant, an antiestrogen drug used to treat hormone-positive breast cancers.

AKT, also known as protein kinase B (PKB) is the collective name of a set of 3 serine/threonine-specific enzymes (protein kinases). ATK enzymes play many vital roles in cellular processes including cell survival, growth, proliferation and metabolism. AKT enzymes promote cell survival by blocking programmed cell death (apoptosis).

Activation of AKT signaling pathway is one of the most commonly activated pathways in breast cancers. AKT is activated by upstream signaling pathways, mutations in AKT1, loss of phosphatase and tensin homolog (PTEN) function and mutations in the catalytic subunit alpha of phosphatidylinositol 3-kinase (PIK3CA).

AKT inhibitors block the activity of all 3 isoforms of AKT enzyme (AKT1, AKT2 and AKT3). AKT inhibitors reduce tumor growth, and risk of disease progression and death more effectively in combination with fulvestrant. Currently, capivasertib is the only drug in this class, approved by the FDA in November 2023.

AKT inhibitors are used in combination with fulvestrant 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-alterations 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.

Side effects of AKT inhibitors include the following:

• Diarrhea
• Nausea
• Oral inflammation (stomatitis)
• Vomiting
• Taste disorder (dysgeusia)
• Indigestion (dyspepsia)
• Adverse skin (cutaneous) reactions including:
  • Rash
  • Hives (urticaria)
  • Eczema
  • Dermatitis
  • Dry skin
  • Itching (pruritus)
  • Fissures and ulcers
  • Redness and discoloration
• Fatigue
• Increase in random and fasting glucose levels (hyperglycemia)
• Blood disorders including:
• Decrease in lymphocyte immune cells
• Decrease in hemoglobin
• Low red blood cell count (anemia)
• Decrease in white blood cells (leukocytes)
• Decrease in neutrophil immune cells
• Decrease in platelets
• Increase in triglycerides
• Increase in liver enzyme alanine aminotransferase (ALT)
• Increase in creatinine
• Decreased corrected calcium
• Decrease in potassium
• Decreased appetite
• Headache
• Urinary tract infection
• Kidney injury
• Pneumonia
• Fever (pyrexia)
• Hypersensitivity reactions
• Second malignancy

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of AKT inhibitors include:

• capivasertib
• Truqap