PARP Inhibitor Therapy

Seven years after ovarian cancer surgery and chemotherapy, 67 percent of women on olaparib tablets were alive. On placebo, 46.5 percent.

Those women all carried a BRCA mutation, and that is the whole logic of PARP inhibitors. These tablets kill cancer cells already crippled in one way of repairing their DNA. Healthy cells survive them. A test decides who benefits, the same test tells a family who else carries the risk, and the treatment itself is taken at home for one to two years. Send us your pathology, any genetic results and your scans, and a medical oncologist will tell you whether a PARP inhibitor fits, which tests are missing, and how a short visit to Istanbul can settle both.

Which cancers do they treat, and what did the trials find?

Four trials.

Between them they show the range of the drugs and the limits of their evidence, from the longest follow-up any PARP inhibitor has had in ovarian cancer to a prostate trial in which most of the comparison group later switched to the drug being tested.

This table scrolls sideways on a narrow screen. Swipe or drag to see every column.

1. Germline BRCA test. A blood or saliva sample tests the BRCA1 and BRCA2 genes you were born with. A positive result qualifies you for a PARP inhibitor in ovarian, breast, prostate and pancreatic cancer, and it matters to your relatives.
2. Tumor BRCA test. The same genes tested in the cancer itself. About a third of BRCA mutations in ovarian cancer are found only in the tumor, so both tests are needed.
3. Homologous recombination deficiency test. A tumor test that measures the genomic scars left by faulty repair, even without a BRCA mutation. In ovarian cancer it identifies patients who gain more from niraparib or from olaparib with bevacizumab.
4. Repair gene panel in prostate cancer. A tumor or blood test for BRCA1, BRCA2, ATM and a dozen other genes. BRCA changes predict the largest benefit.

At 7 years, 67.0 percent of olaparib patients versus 46.5 percent of placebo patients were alive, and 45.3 percent versus 20.6 percent were alive and had not received a first subsequent treatment.

SOLO1 seven-year report, Journal of Clinical Oncology, 2023

The last figures brought a word into advanced ovarian cancer that oncologists had avoided. Nearly half the women on olaparib had needed no further treatment seven years after starting it, and the authors wrote of an enhanced potential for cure. The honest reading keeps both halves. The survival advantage is large and consistent, and by the trial's own pre-set rule it did not reach statistical significance, because the rule demanded an exceptionally strict threshold.

The BRCA result and your family

Germline BRCA mutations are inherited, and each parent, sibling and child of a carrier has a one-in-two chance of carrying it too. For relatives the test serves prevention. A woman who knows she carries BRCA1 can be offered intensive breast screening and removal of the ovaries at the age when the risk rises, and a man who carries BRCA2 can have prostate screening earlier. A result that qualifies you for olaparib should therefore start a second conversation. The genetic counselor leads it, and it decides who else in the family is offered the test.

1. A genetic counseling appointment explains the result, the risks to you beyond this cancer, and the options.
2. A letter for relatives names the exact mutation, which lets their own laboratory test for it quickly and at lower cost.
3. Relatives decide for themselves whether to be tested. Nobody is tested without consent.
4. A carrier relative is offered screening and prevention plans suited to age and sex.

The 3-year invasive disease-free survival was 85.9 percent in the olaparib group and 77.1 percent in the placebo group.

OlympiA, early breast cancer with a germline BRCA mutation, New England Journal of Medicine, 2021

• Anyone with ovarian, fallopian tube or peritoneal cancer, whatever the family history.
• Breast cancer diagnosed young, triple-negative breast cancer, breast cancer in a man, or breast cancer with a strong family history.
• Metastatic prostate cancer and pancreatic cancer.
• Relatives of anyone found to carry a BRCA mutation.

How the tablets are taken

Taking the tablets is simple. Watching them is not. Olaparib means two tablets twice a day, niraparib one dose at bedtime, with or without food. In ovarian cancer the drug starts within eight weeks of the last chemotherapy cycle and continues for two years with olaparib, or three with niraparib, or until the cancer returns. In early breast cancer it runs for one year. In metastatic prostate and breast cancer it continues while it works. When side effects build, the dose comes down and the treatment continues, and patients who need a reduction keep the benefit at the lower dose.