II. Indications
-
Breast Cancer (PIK3CA mutation, HR positive, HER2 negative, metastatic)
- Alpelisib
-
Follicular Lymphoma (relapsed)
- Copanlisib
- Duvelisib
- Idelalisib
-
Chronic Lymphocytic Leukemia (relapsed or refractory)
- Duvelisib
- Idelalisib
- Small Lymphocytic Leukemia (relapsed or refractory)
- Duvelisib
- Idelalisib
III. Mechanism
-
Phosphatidylinositol 3-Kinase Catalytic Alpha (PIK3CA)
- PIK3CA gene encodes for Phosphatidylinositol 3-kinases (PI3K), key to cell growth, development and survival
-
Phosphatidylinositol 3-kinase (PI3K)
- Growth factors bind and activate PI3K Tyrosine Kinase, triggering synthesis of PIP3 as a secondary messenger
- PIP3 drives many cell processes, including growth, development, apoptosis, adhesion and motility
- PI3K Inhibitors
- Block various subunits (alpha, delta) to impact cancer growth, function, proliferation and antineoplastic resistance
IV. Medications
- Alpelisib (Piqray)
- PI3K Inhibitor of the alpha subunit
- Risk of Hypersensitivity Reaction, severe rash (SJ/TEN), Hyperglycemia, pneumonitis, severe Diarrhea
- Take with food (absorption increased >70%)
- Avoid with Strong CYP3A4 Inducers
- Copanlisib (Aliqopa)
- PI3K Inhibitor of the alpha and delta subunits
- Inhibits B-Cell receptor-mediated signaling and B-Cell chemotaxis
- Also inhibits NFkB signaling
- Risk of Neutropenia, severe infections, Hyperglycemia, Severe Hypertension, pneumonitis and severe rash (SJ/TEN)
- Consider PJP Prophylaxis
- Avoid with Strong CYP3A4 Inducers, and reduce dose with strong CYP3A4 inhibitors
- Duvelisib (Copiktra)
- PI3K Inhibitor of the alpha and delta subunits
- Risk of colitis and severe Diarrhea, Neutropenia, severe infections, pneumonitis, hepatotoxicity and severe rash (SJ/TEN)
- Consider PJP Prophylaxis
- Idelalisib (Zydelig)
- PI3K Inhibitor of the delta subunit
- Risk of colitis and severe Diarrhea, Neutropenia, severe infections, pneumonitis, hepatotoxicity, Hypersensitivity, severe rash
V. Dosing
- See other references for disease specific dosing protocols
VI. Safety
- Avoid in Lactation
- Continue to avoid Lactation for at least 1 month after last dose of Duvelisib
- Avoid in pregnancy (all trimesters, pregnancy category X)
- Use reliable Contraception
- Monitoring
- Complete Blood Count
- Blood Glucose
- Blood Pressure (Copanlisib)
- Liver Function Tests (Idelalisib, Duvelisib)
VII. Adverse Effects
- Severe Hypersensitivity Reaction (Alpelisib, Idelalisib)
- Severe dermatologic reactions (Alpelisib, Copanlisib, Duvelisib, Idelalisib)
- Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis
- DRESS Syndrome (Duvelisib)
- Hyperglycemia including Ketoacidosis (Alpelisib, Copanlisib)
- Severe Diarrhea or colitis (Alpelisib, Duvelisib, Idelalisib)
- Pneumonitis or Interstitial Lung Disease (Alpelisib, Copanlisib, Idelalisib)
-
Neutropenia and Severe Infections, esp. Pneumonia, Sepsis (Copanlisib, Duvelisib, Idelalisib)
- Consider PJP Prophylaxis
- Severe Hypertension (Copanlisib)
- Hepatotoxicity with transaminase increase (Idelalisib, Duvelisib)
VIII. Drug Interactions
- Strong CYP3A4 Inducers
- Avoid with Alpelisib, Copanlisib, Duvelisib
- Strong CYP3A4 Inhibitors
- Decrease Copanlisib or Duvelisib dose
-
CYP3A4 Substrates with narrow Therapeutic Index
- Observe for toxicity with Duvelisib
- BCRP Inhibitors
- Avoid with Alpelisib
IX. Resources
- Alpelisib (DailyMed)
- Copanlisib (DailyMed)
- Duvelisib (DailyMed)
- Idelalisib (DailyMed)