Olaparib, known by the brand name Lynparza, is a targeted cancer therapy and a PARP inhibitor. It treats certain cancers by interfering with their ability to repair damaged DNA. This medication represents a significant advancement in personalized medicine, focusing on specific vulnerabilities within cancer cells rather than broadly affecting all rapidly dividing cells.
How Olaparib Works
Poly (ADP-ribose) polymerase (PARP) enzymes are proteins that repair damaged DNA. Cells, including cancer cells, rely on these repair mechanisms to maintain genetic integrity and survive. PARP inhibitors like olaparib work by blocking PARP enzyme activity, preventing cancer cells from effectively repairing single-strand DNA breaks.
When single-strand DNA breaks occur and PARP is inhibited, these breaks can escalate into double-strand DNA breaks during cell replication. Healthy cells have other DNA repair pathways, such as homologous recombination, which can fix these breaks. However, some cancer cells have existing defects in these alternative repair pathways, particularly those with BRCA1 or BRCA2 gene mutations.
This leads to a concept known as “synthetic lethality.” Synthetic lethality describes a situation where the individual loss of either of two genes or pathways is compatible with cell survival, but the simultaneous loss of both results in cell death. Cancer cells with BRCA mutations are already deficient in homologous recombination repair. When olaparib inhibits PARP, these cells lose their primary backup DNA repair mechanism, leading to an overwhelming accumulation of unrepaired DNA damage. This extensive damage triggers programmed cell death in the cancer cells, while healthy cells, with their intact homologous recombination pathway, can still repair their DNA and survive.
Cancers Treated with Olaparib
Olaparib is approved for treating several types of cancer, especially those associated with specific genetic mutations that affect DNA repair. It is used for ovarian cancer, including advanced cases with BRCA mutations, either as a first-line maintenance treatment or for recurrent disease after platinum-based chemotherapy. It can also be used in combination with bevacizumab for advanced ovarian cancer with genomic instability or BRCA mutations.
In breast cancer, olaparib is approved for HER2-negative, germline BRCA-mutated metastatic breast cancer, often after prior chemotherapy. It also serves as an adjuvant treatment for high-risk early-stage HER2-negative breast cancer with germline BRCA mutations, following chemotherapy.
For pancreatic cancer, olaparib serves as maintenance therapy for metastatic cases with germline BRCA mutations that have not progressed after platinum-based chemotherapy.
Olaparib is also utilized in prostate cancer, specifically for metastatic castration-resistant prostate cancer that has mutations in homologous recombination repair (HRR) genes. This includes situations where the cancer has progressed after treatments like enzalutamide or abiraterone. Additionally, it can be used in combination with abiraterone and prednisone for certain metastatic castration-resistant prostate cancer cases with BRCA mutations.
What to Know About Olaparib Treatment
Olaparib is administered orally, as tablets taken twice a day, approximately 12 hours apart. Patients swallow the tablets whole, and they can be taken with or without food. The duration of treatment varies and is determined by the treating physician based on the individual’s condition and response.
Common side effects associated with olaparib treatment include nausea, fatigue, vomiting, abdominal pain, and anemia (low red blood cell counts). Other frequently reported side effects can include diarrhea, decreased appetite, headache, and dizziness. These side effects can vary in severity among individuals, and healthcare providers often prescribe medications to help manage symptoms like nausea and vomiting.
Genetic testing is an important step before starting olaparib. This testing identifies specific genetic mutations, such as BRCA1/2 or homologous recombination deficiency (HRD), which indicate that a patient’s cancer is more likely to respond to olaparib. This personalized approach ensures the medication is directed towards patients who stand to benefit most from its targeted mechanism.
During treatment, regular monitoring is necessary to assess how a patient is responding and to manage any potential side effects. This involves routine blood tests to check blood cell counts, as well as liver and kidney function. Monitoring helps detect potential complications like myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), which are serious, albeit less common, bone marrow problems observed in some patients, particularly those with a history of extensive chemotherapy or radiotherapy.