Copanlisib, sold under the brand name Aliqopa, is a medication used to treat certain hematologic cancers. It works by inhibiting specific signaling pathways within cancer cells to slow or stop their growth. Because Copanlisib acts on biological processes throughout the body, treatment requires careful monitoring for side effects. This article explains the drug’s approved applications, mechanism of action, adverse effects, and administration.
Approved Medical Applications
Copanlisib received regulatory approval for the treatment of adult patients diagnosed with relapsed follicular lymphoma (FL). Follicular lymphoma is a form of non-Hodgkin lymphoma, which is a cancer that affects the white blood cells called lymphocytes. The drug is specifically indicated for patients whose disease has returned after they have already received at least two prior systemic therapies.
The initial approval for this use was granted on an accelerated basis by the U.S. Food and Drug Administration (FDA). Accelerated approval is given to drugs that treat serious conditions based on data that predicts a clinical benefit. This decision was primarily based on the overall response rate observed in a phase II clinical trial.
However, the manufacturer announced a voluntary withdrawal of the U.S. New Drug Application in November 2023 because the required confirmatory study did not meet its primary endpoint. Despite this withdrawal, the drug remains a subject of research for other hematologic malignancies and solid tumors.
Targeting Cancer Growth
Copanlisib functions as an inhibitor of phosphatidylinositol 3-kinase (PI3K). PI3K is a family of enzymes that play a central role in a signaling network responsible for cellular processes like growth, proliferation, survival, and migration. In many cancers, including lymphomas, this PI3K pathway is overactive, continuously signaling the cancer cells to multiply and resist natural cell death.
The drug is classified as a pan-Class I PI3K inhibitor, meaning it targets multiple forms of the PI3K enzyme. Copanlisib demonstrates preferential activity against the alpha and delta isoforms of PI3K. The PI3K-delta isoform is primarily found in blood cells, making its inhibition particularly effective in B-cell malignancies like follicular lymphoma.
By binding to the enzyme’s active site, Copanlisib blocks the kinase activity of PI3K, thus interrupting the downstream signaling cascade. This blockage leads to the suppression of pathways, such as the AKT/mTOR pathway, which are essential for cancer cell survival. The result is the induction of apoptosis (programmed cell death) and the inhibition of uncontrolled cell proliferation in the malignant B-cells.
Targeting the PI3K-alpha isoform also contributes to the drug’s activity, although its inhibition is linked to some of the specific side effects observed with the therapy. This mechanism aims to starve the cancer cells of the survival signals they rely on, leading to tumor regression.
Understanding Potential Adverse Effects
Treatment with Copanlisib requires extensive patient monitoring due to several adverse effects. The most common side effects reported were:
- Hyperglycemia (high blood sugar)
- Diarrhea
- Fatigue
- Hypertension (high blood pressure)
Hyperglycemia, a frequent occurrence, is considered an expected consequence of inhibiting the PI3K-alpha isoform, which is involved in insulin signaling.
Hyperglycemia and hypertension are often infusion-related, meaning they tend to occur or worsen around the time of treatment. They require pre-infusion monitoring of blood glucose and blood pressure. Healthcare providers must ensure optimal blood glucose control is achieved before each dose is administered, and if blood pressure is too high, the infusion may be withheld. Management of these effects may include medication adjustments, dose reduction of Copanlisib, or temporary discontinuation of the drug.
The drug can also cause hematologic toxicity, which refers to adverse effects on the blood cell counts. The most frequent hematologic issues include neutropenia (low white blood cell count) and thrombocytopenia (low platelet count). Neutropenia increases the risk of serious infections, and blood counts must be checked regularly, often at least weekly.
Serious infections, particularly lower respiratory tract infections like pneumonia, are a complication requiring close observation. Non-infectious pneumonitis (inflammation of the lungs) is another serious side effect. Patients experiencing new or worsening cough or shortness of breath must notify their care team immediately.
Treatment Protocol and Delivery
Copanlisib is administered intravenously (IV) via infusion in a clinical setting by a healthcare professional. The infusion takes approximately one hour to complete. The drug must be mixed only with 0.9% sodium chloride solution before administration.
The treatment follows an intermittent dosing schedule based on a 28-day cycle. Patients receive the standard dose on Day 1, Day 8, and Day 15 of the cycle, followed by a one-week rest period. This schedule is designed to help manage common side effects, such as temporary spikes in blood sugar and blood pressure that occur post-infusion.
Treatment with Copanlisib is continued for as long as the patient is receiving benefit and can tolerate the adverse effects. If significant toxicity occurs, the dose may be reduced from 60 mg to 45 mg, and then potentially to 30 mg, or the drug may be discontinued entirely.