Lynparza (Olaparib): What It Is and What to Expect

Cells repair broken DNA all day long. They have more than one repair system. A protein called PARP runs one of them.

Olaparib blocks PARP. In a healthy cell that is survivable, because a backup system takes over. In a cancer cell whose backup is already broken — which is what a BRCA gene change means — losing PARP as well leaves the damage unrepaired. The cell dies. Healthy cells, with both systems, mostly carry on.

Lynparza is the brand name; olaparib is the generic name.

Every approved use of olaparib names an FDA-approved companion test. This is unusual, and it is worth understanding before your first appointment about it.

The test looks at BRCA1 and BRCA2, and for some uses at a wider set of repair genes or at a score called homologous recombination deficiency. The change can be one you inherited, or one that appeared in the tumor itself. Which test you need depends on the cancer.

If the test does not show the change, olaparib is not the right drug. That is not a judgment about you or your cancer. It is how this drug works.

Most olaparib approvals are for maintenance. That word confuses people, so it is worth being clear.

Maintenance means you have already had platinum chemotherapy, and it worked. Olaparib then starts, and its job is to hold that result for as long as possible. You are not waiting to see a tumor shrink, because the shrinking already happened. This changes what "is it working" means, and it changes how scans get read.

• Ovarian, fallopian tube and primary peritoneal cancer. Maintenance after first-line platinum chemotherapy with a BRCA change. Maintenance with bevacizumab where the cancer is HRD-positive. Maintenance in BRCA-mutated cancer that has come back.
• Breast cancer. After chemotherapy in high-risk early disease with an inherited BRCA change. Also for HER2-negative metastatic breast cancer with an inherited BRCA change.
• Pancreatic cancer. Maintenance in metastatic disease with an inherited BRCA change, after at least 16 weeks of platinum chemotherapy.
• Prostate cancer. For castration-resistant disease with a repair-gene change after enzalutamide or abiraterone. Also with abiraterone and a steroid where there is a BRCA change.

The usual strength on the label is 300 mg by mouth twice a day, roughly twelve hours apart, with or without food. Take what your own prescription says, not what this page says — teams start some people lower, and reduce the dose later for blood counts, kidney function or side effects. Swallow the tablets whole. Do not chew, crush or split them. If you miss a dose, do not double up; take the next one at its normal time.

Skip grapefruit, grapefruit juice, Seville oranges and their juice while you are on it. They slow the enzyme that clears olaparib, so more drug stays in your blood.

Several prescription drugs do the same thing, including some antifungals and antibiotics. Your team may lower the olaparib dose rather than stop the other medicine. Let them check anything new before you start it.

Tiredness, nausea and a low appetite are the common effects. They often ease after the first weeks, and anti-sickness medicine helps.

Three things need reporting rather than waiting.

Blood counts are checked monthly. A small number of people treated with olaparib have developed myelodysplastic syndrome or acute myeloid leukemia — a serious bone marrow cancer. Counts that keep falling are how it gets caught.

New breathlessness, a cough or a fever may mean inflammation in the lungs. Treatment is paused while that is checked.

Pain, swelling or warmth in a leg, or sudden breathlessness, may mean a clot. In the prostate cancer trials, clots were markedly more common with olaparib than without.

Liver injury has also been reported. Belly discomfort, dark urine or yellowing skin should be phoned in the same day.

• Call 911 or go to an emergency department if breathlessness comes on abruptly, it hurts to breathe in, or you cough up blood. A clot in the lung behaves like this, and clots were more common on olaparib in the prostate cancer trials.
• Call your cancer team within the hour, day or night, if your temperature reaches 100.4°F (38°C) or you feel hot, shaky and unwell. Olaparib lowers white cells, and CDC treats a fever during cancer treatment as a medical emergency, because infection can move fast when counts are low. Say on the phone that you are on cancer treatment. If you cannot get hold of them, go to an emergency department instead of waiting, and do not take fever medicine first unless your team has told you to.
• Call your care team the same day if one calf or thigh is swollen, warm and sore, or your belly aches with dark urine or yellow skin.
• Call your care team the same day if a dry cough or breathlessness builds up over days, or you get short of breath doing things you managed last week. Lung inflammation (pneumonitis) starts quietly, and olaparib is usually paused while it is checked.
• Call your care team within a day or two if you are getting more tired week by week, bruising easily, or bleeding from the gums or nose, especially around your monthly blood count.

• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa
• https://www.cdc.gov/cancer-preventing-infections/patients/fever.html
• https://www.cancer.gov/about-cancer/treatment/drugs/olaparib