Genetic test determines maintenance treatment for ovarian cancer

PARP inhibitors (PARPi) have been used for several years now as a highly effective maintenance treatment in a group of patients with ovarian cancer. Using PARPi relapse after surgery and chemotherapy can be prevented or delayed. Researchers at UZ Leuven and KU Leuven have, in collaboration with the 'Vlaams Instituut voor Biotechnologie' (VIB) developed a test to determine which patients will respond to PARPi. This test helps to avoid unnecessary expensive treatments and side effects. The test is based on the analysis of the genetic profile of the patient's tumour cells. Starting in May2023, UZ Leuven will be the first hospital in Belgium to offer this accredited test.

Each year, approximately 800 women in Belgium are diagnosed with ovarian cancer. The diagnosis is often made at an advanced stage. The standard treatment consists of chemotherapy and surgery, but despite these efforts, 8 out of 10 women with advanced ovarian cancer relapse within 2 to 3 years. In recent years, besides the standard treatment, several new, more targeted therapies have been approved, including PARPi. These tablets can delay or even prevent the recurrence of the disease after treatment.

However, this medication is only effective in about halve of the patient population. Therefore, researchers in Leuven have developed an HRD test: a genetic test, based on tumour tissue taken during surgery, to indicate which patients will respond to the treatment. HRD stands for 'homologous recombination deficiency', one of the mechanisms by which the human body deals with DNA errors. When many errors are not, or incorrectly, repaired, this can be detected by the Leuven HRD test, which shows whether the cancer cells are susceptible to PARP medication.

Use outside a research context

Up to now the test was performed via a collaboration with a company located in the United States and associated with a significant cost. The shipment of samples to the USA also created logistic problems and increased waiting times. UZ Leuven is now the first European hospital that will implement an own, unique and cheaper version of the test outside of a research context. A BELAC accreditation, based on internationally recognized criteria, was recently obtained for this goal. BELAC is the sole Belgian accredition agency responsible for the evaluation of the tests performed in Belgian laboratories. Thanks to this accreditation the in-house developed HRD test receives an internationally recognized quality label, which is a first in the European hospital community. The patient is not the only beneficiary of this, since the test and analysis can be done in Belgium it leads to a significant cost decrease. Patients additionally do not have to be treated unnecessarily with PARPi in case the test shows that the treatment won't be effective. This allows them to switch to other, more promising treatments, sooner. Prof. dr. Toon Van Gorp, medical specialist gynaecological oncologie UZ Leuven: "Thanks to this test we can avoid unnecesary expensive treatments and side effects. This is excellent news for patients with ovarian cancer and the result of a close collaboration between out hospital's physicians and researchers from the VIB and KU Leuven." Prof. Diether Lambrechts (oncological researcher VIB-KU Leuven) and prof. Hilde Brems (molecular genetics KU/UZ Leuven): "The development of this test is a perfect example of how translational research enables the passage and quick translation of knowledge and new technologies to diagnosis and treatments which are beneficial for the patients."

Negative testing

Treatment with PARPi has, like any other therapy, side effects (e.g. anemia, nausea and fatigue). If the physicians know on beforehand that a patient would not be eligible for this therapy they don't have to expose the patient to these adverse effects and could start an alternative treatment immediately. Patients which test negative are therefore not left behind since they can receive other treatments. Not being eligible for maintenance treatment with PARPi is therefore not automatically bad news.