Talazoparib is a targeted cancer therapy sold under the brand name Talzenna. It belongs to a class of drugs known as PARP inhibitors, which are designed to exploit specific weaknesses in cancer cells. As a form of precision medicine, it is prescribed for individuals whose cancer has specific genetic traits, targeting the tumor’s unique molecular characteristics.
How Talazoparib Works
Within our cells, enzymes called poly (ADP-ribose) polymerase, or PARP, detect single-strand breaks in the DNA and signal for repairs. This process is a constant part of maintaining cellular health. Talazoparib works by inhibiting these PARP enzymes.
Talazoparib has two primary functions. It blocks the enzymatic activity of PARP, preventing the initial signaling for DNA repair. More potently, it also “traps” the PARP enzyme onto the DNA damage site, creating a physical roadblock that prevents the repair machinery from accessing the break. This trapping action turns a simple, repairable single-strand break into a more complex and lethal double-strand break during cell division.
This mechanism is effective in cancer cells with a mutation in their BRCA1 or BRCA2 genes. Healthy cells have two systems for repairing DNA: the PARP-driven pathway for single-strand breaks and a separate pathway called homologous recombination for double-strand breaks, which relies on functional BRCA proteins. In cancer cells with a BRCA mutation, the homologous recombination pathway is already defective. By using talazoparib to disable the PARP pathway, both DNA repair systems are shut down, a concept known as “synthetic lethality.” The accumulation of unrepaired DNA damage leads to the targeted death of the cancer cell.
Approved Medical Uses
The U.S. Food and Drug Administration (FDA) has approved talazoparib for specific cancers with certain genetic markers. Its primary approval is for the treatment of adults with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative breast cancer that is either locally advanced or metastatic. “Germline” indicates the BRCA mutation is inherited and present in all cells of the body, not just the tumor.
Patient eligibility is determined by a specific genetic test. The FDA requires an approved companion diagnostic test, such as the BRACAnalysis CDx, to confirm the presence of a qualifying BRCA1 or BRCA2 mutation before starting treatment. This ensures the therapy is directed at cancers with the specific vulnerability the drug exploits.
Talazoparib is also approved in combination with the drug enzalutamide for adult patients with a certain type of metastatic prostate cancer. This approval is for patients with metastatic castration-resistant prostate cancer (mCRPC) that has mutations in homologous recombination repair (HRR) genes. This category of mutations includes BRCA mutations.
Administration and Patient Monitoring
Talazoparib is an oral capsule taken once daily, with or without food. The capsule should be swallowed whole and not opened or dissolved. If a dose is missed or the patient vomits after taking it, they should wait until the next scheduled time and not take an extra dose. The standard dose for breast cancer is 1 mg daily.
Patient monitoring is required due to talazoparib’s effects on bone marrow. Before a patient begins the medication, a baseline complete blood count (CBC) is required to assess their levels of red blood cells, white blood cells, and platelets. This monitoring must continue with monthly blood tests to watch for the development of myelosuppression, a condition where bone marrow activity is decreased.
Based on the results of these regular blood tests, a patient’s dosage may need to be adjusted. If a patient’s hemoglobin, neutrophil, or platelet counts fall below certain thresholds, the doctor may temporarily pause treatment. Once the blood counts recover to a safe level, treatment can be resumed, often at a reduced dose to better manage the side effects.
Common Side Effects
The most common side effects of talazoparib are blood-related due to its impact on bone marrow. Myelosuppression can lead to anemia, causing fatigue, weakness, and shortness of breath. It also causes neutropenia, which increases infection risk, and thrombocytopenia, which can lead to easier bruising and bleeding.
Gastrointestinal issues are also common among patients taking talazoparib. Nausea, vomiting, and diarrhea are frequently experienced, which can lead to a decreased appetite. These symptoms may be managed with supportive care. Other widely reported side effects include headaches and alopecia, or hair loss.
Talazoparib carries a risk for more serious, though less common, conditions like Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML), which are types of bone marrow cancers. Patients are advised to maintain open communication with their healthcare team. Reporting any new or worsening side effects promptly is needed for safe management of the treatment.