Medical Oncology and Genetics
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.
67% vs 46.5%
Alive at seven years, ovarian cancer, BRCA, olaparib against placebo
85.9% vs 77.1%
Free of invasive disease at three years, early breast cancer
Tablets
Taken at home, once or twice a day
Free
Review of your pathology and genetic results
Free consultation
Four PARP inhibitors are in use, all of them tablets or capsules. They differ in the cancers they are licensed for, in whether they need a BRCA mutation or a broader DNA repair defect, and in their side effects on the blood count.
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.
Randomized trials of PARP inhibitors
| Cancer and setting |
Trial |
Compared |
Result |
| Ovarian cancer, newly diagnosed, BRCA mutation, after response to platinum |
SOLO1, 391 patients, seven-year report in the Journal of Clinical Oncology |
Olaparib or placebo for up to two years |
Alive at seven years 67.0 against 46.5 percent. Alive without any further treatment 45.3 against 20.6 percent. The survival difference missed its strict statistical threshold |
| Ovarian cancer, newly diagnosed, with or without BRCA |
PRIMA, 733 patients, New England Journal of Medicine 2019 |
Niraparib or placebo |
Median time without progression 21.9 against 10.4 months in tumors with a repair defect, 13.8 against 8.2 in all patients |
| Early breast cancer, germline BRCA, HER2-negative, high risk, after chemotherapy and surgery |
OlympiA, 1,836 patients, New England Journal of Medicine 2021 |
Olaparib or placebo for one year |
Free of invasive disease at three years 85.9 against 77.1 percent. Free of distant spread 87.5 against 80.4 percent |
| Metastatic prostate cancer, DNA repair gene change, after a new hormone drug |
PROfound, 387 patients, New England Journal of Medicine 2020 |
Olaparib or a second hormone drug |
In BRCA1, BRCA2 or ATM changes, median survival 19.1 against 14.7 months, although two thirds of the control group later switched to olaparib |
- 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.
- 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.
- 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.
- 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.
- A genetic counseling appointment explains the result, the risks to you beyond this cancer, and the options.
- A letter for relatives names the exact mutation, which lets their own laboratory test for it quickly and at lower cost.
- Relatives decide for themselves whether to be tested. Nobody is tested without consent.
- 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.
What are the side effects, how is treatment watched, and how is it arranged from abroad?
Anemia, low platelets and low white cells
The blood count is where PARP inhibitors bite. In the PRIMA trial of niraparib, grade 3 or worse anemia occurred in 31.0 percent, low platelets in 28.7 percent and low white cells in 12.8 percent, and there were no treatment-related deaths. Olaparib spares platelets more. Anemia is its main effect.
Most of these changes appear in the first three months. Pausing the drug for a week or two, restarting at a lower dose and, for anemia, transfusion manage them. Weekly counts in the first month are the rule.
Nausea, tiredness and taste change
Nausea comes in the first weeks and then settles for the majority. Over the long run, tiredness draws the most complaints. Taking the tablets with food, an anti-sickness tablet before them for the first weeks, and a nap in the afternoon are the practical answers.
Blood cancers and other rare effects
Some patients, few in number, develop myelodysplastic syndrome or acute myeloid leukemia, bone marrow cancers linked to earlier chemotherapy and to PARP inhibition. In the seven-year SOLO1 report the rate remained low, and new cancers were balanced between the olaparib and placebo groups. A blood count that fails to recover after a pause leads to a bone marrow test.
Niraparib can raise blood pressure, which is checked at each visit. Olaparib and niraparib interact with some antibiotics, antifungal drugs and seizure medicines, and every new prescription should be checked with the oncology pharmacist.
1
The first month
Blood count every week, blood pressure with niraparib, and a phone or video review of nausea and energy. Your local laboratory can do the counts and send them to the coordinator.
2
Months two to twelve
Blood count every month, clinical review every three months, and scans at intervals set by the cancer, every three to six months in most cases.
3
After the course
In ovarian and early breast cancer the drug stops at the planned time if there is no disease. Follow-up continues with your own oncologist, and the family testing plan continues with the genetic counselor.
Days in Istanbul
No hospital stay is needed. The visit covers everything around it, in five to seven working days. The first day brings the consultation and the blood tests. The germline test is drawn the same day, and if the tumor has not been tested, the pathology blocks are sent from home or the biopsy slides are reviewed here. Genetic counseling and the tumor board fall within the week. Most patients leave with a first month's supply and a written plan, and continue at home. Results that take longer, such as the homologous recombination test, arrive by e-mail and WhatsApp and are discussed by video.
Fly whenever you like. The tablets travel in hand luggage with a doctor's letter, in their original packs, and a supply for the whole period away plus a week is sensible, since customs rules for cancer drugs differ from one country to the next and a missed week is harder to recover than a delayed flight.
What decides the cost
Three things. Tests come first, since a germline panel, a tumor BRCA test, a homologous recombination test and a prostate repair gene panel are separate items with different prices, and the reply to your file lists which ones are missing. The drug, second, priced by the month and taken for one to three years, which makes it the largest cost of all and the one most worth checking against what your own health system will reimburse once the result is in hand. Monitoring, third, with monthly blood counts, scans and transfusions if anemia requires them. Consultations, genetic counseling and the tumor board are paid once. Hospitals in Istanbul do not publish packages for this treatment, and the online price lists for cancer drugs mostly concern infusions. A written quote should separate the tests from the drug.
Your own figure follows the free review.
Language, companions and follow-up at home
One coordinator from the international patients team is assigned from your first message and stays with you through the course. The team works in English, Arabic, French, Russian, Serbian, Romanian and Spanish and arranges interpreting in other languages on request, and genetic counseling through an interpreter is arranged with extra time, because the conversation matters to your whole family. An invitation letter naming the hospital and the treating oncologist is sent ten days before travel. The international patients office arranges the airport transfer and the hotel for you and a companion. Halal, vegetarian and diabetic meals are available, a prayer room is on site, and a request for a female doctor is passed to the department and met wherever the rota allows. Surgery, radiotherapy, gynecologic oncology and medical oncology share one site. No second hospital is needed. Back home, the coordinator stays reachable on the same WhatsApp number, blood counts go to the treating oncologist, and a symptom such as unusual bruising, breathlessness or fever goes to a local doctor the same day.
PARP inhibitor FAQ
What is a PARP inhibitor?
A tablet that blocks PARP, an enzyme that repairs small breaks in DNA. Cancer cells that have lost another repair system, most often through a BRCA mutation, die when PARP is blocked, while healthy cells survive.
Do I need a BRCA mutation to receive a PARP inhibitor?
Not always. In ovarian cancer, niraparib works with or without a BRCA mutation, most in tumors with a repair defect. In breast and pancreatic cancer a germline BRCA mutation is required, and in prostate cancer a change in one of several repair genes.
How effective is olaparib in ovarian cancer?
In SOLO1, 67 percent of women with a BRCA mutation were alive at seven years with olaparib against 46.5 percent with placebo, and 45.3 percent against 20.6 percent had needed no further treatment.
What are the main side effects?
Anemia, low platelets and low white cells, nausea and tiredness. Most appear in the first three months and are managed by pausing the drug and restarting at a lower dose. Bone marrow cancers are rare.
How long do I need to stay in Istanbul?
Five to seven working days for the consultation, tests, genetic counseling and the plan. The tablets are then taken at home, with blood counts done locally.
Should my family be tested?
If you carry a germline BRCA mutation, each parent, sibling and child has a one-in-two chance of carrying it. Genetic counseling helps them decide, and the letter naming your mutation makes their testing quick.
Results support the use of maintenance olaparib to achieve long-term remission in this setting, and the potential for cure may also be enhanced.
Conclusion of the SOLO1 seven-year report, Journal of Clinical Oncology, 2023
References
- DiSilvestro P, Banerjee S, Colombo N, et al. Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. Journal of Clinical Oncology. 2023;41(3):609-617.
- Gonzalez-Martin A, Pothuri B, Vergote I, et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine. 2019;381(25):2391-2402.
- Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. New England Journal of Medicine. 2021;384(25):2394-2405.
- de Bono J, Mateo J, Fizazi K, et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer. New England Journal of Medicine. 2020;382(22):2091-2102.
- Hussain M, Mateo J, Fizazi K, et al. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. New England Journal of Medicine. 2020;383(24):2345-2357.
