Optimizing the Timing of Genetic Testing in Advanced Ovarian Cancer

Although multiple factors might impact the utility and eligibility of PARP inhibition in patients with newly diagnosed advanced ovarian cancer, the most important ones may relate to gene alterations found during genetic blood testing, according to Melissa K. Frey, MD.

Frey, an associate professor of Obstetrics and Gynecology in the Division of Gynecologic Oncology and director of Genetics and Personalized Cancer Prevention Program at Weill Cornell Medicine, discussed how the timing of genetic testing may influence therapeutic decision-making regarding the use of PARP inhibitors in patients with advanced ovarian cancer in a conversation with CancerNetwork®. She began by highlighting that genetic counseling provides information beyond tumor causation and potential indications for other cancers as well as risk factors for family members, which may also impact treatment decision-making.

She emphasized that early testing is imperative so that a treatment plan can be developed as soon as possible. Furthermore, Frey discussed the importance of germline testing for genetic aberrations, which identifies patients who may best benefit from PARP inhibitors. She noted that somatic mutations in the Fanconi anemia pathway genes, however, may not show up on germline testing.

For these mutations, she remarked, tumor samples may be required but can only be retrieved until after surgery. She stressed that blood samples collected before an operation and tumor samples collected afterwards are needed to undergo genetic testing.

Transcript:

For ovarian cancer, it is one of the solid tumors where genetic testing is not [only] providing information on causation of the tumor and important implications for other cancers and family members. It directly impacts treatment decisions. The PARP inhibitor is one of the best examples of precision or personalized medicine, which is based on specific characteristics of the tumor or of the germline cells. In general, we want that genetic testing to happen as soon as possible so that the physician can be armed with that information to make a treatment plan and to think about including a PARP inhibitor in a treatment algorithm.

Now, what can be a bit complicated is that the utility and patient eligibility for PARP inhibitors depend on many things, but what we found is having a homologous recombination deficiency [HRD] or having a mutation in BRCA1, BRCA2, or similar genes is most important. But that can [only be in] the tumor or in the germline, and so we end up doing genetic testing, often on blood. That’s what we call germline, or the inherited predisposition to these cancer syndromes. Also, we know that 5% or more of patients can have a somatic mutation in one of these Fanconi anemia pathway genes that may also have caused the mutation, [which] would make the patient a good candidate for a PARP inhibitor, but this is a patient who will not have germline testing [positivity].

That speaks to the fact that we need to have access to the patient’s blood, and we need to have access to patient tumor. That may then require, especially for a patient who is having neoadjuvant treatment, [having] to wait until surgery to have sufficient tumor to sample. Finally, I said somatic mutations, but it’s not just mutations; it’s also the HRD signature in general, which, again, we need at this current point in time. That affects pre-operative or post-operative testing. It is access to the needed material to do the comprehensive genetic testing.