Lyndsay Willmott, MD, gynecologic oncologist, Arizona Oncology, discusses the expanding role for genomic testing in ovarian cancer.
Companion diagnostics are available to identify patients with homologous recombination deficiency (HRD)–positive ovarian cancer, Willmott says. However, not all patients within this subgroup are being captured with current testing options. As such, genomic testing will continue to evolve to better identify the genomic scarring associated with this disease subtype, Willmott explains. 

Additionally, genomic assays are available to identify germline mutations that span several different genes, Willmott adds.

Most clinicians utilize HRD testing routinely, as it captures the largest pool of patients with ovarian cancer, Willmott continues. Additionally, reflex testing can determine whether HRD positivity is related to an underlying germline mutation, Willmott says. Finally, germline mutations are important to uncover so that a patient’s family members can be tested if indicated, Willmott concludes.

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Lyndsay Willmott, MD, discusses the expanding role for genomic testing in ovarian cancer. 


Dr. Willmott on Expanding Genomic Testing in Ovarian Cancer

Lyndsay Willmott, MD, gynecologic oncologist, Arizona Oncology, discusses the importance of genetic testing in ovarian cancer.

When treating patients with ovarian cancer, genetic testing is one of the easiest tools to incorporate into clinical practice to help guide treatment decisions, according to Willmott. However, because genetic counselors are scarce in some areas, it is important to be an informed advocate for genetic testing so that its use is initiated in the frontline, Willmott says. Additionally, educating patients on the importance of genetic testing can serve to overcome hesitancy and empower them with respect to treatment decisions, Willmott adds. 

Moreover, it has been shown that patients with a 

 mutation may perform better with certain agents, according to Willmott. Although this might not be universal, it is important to counsel patients about the link between mutational status and their available treatment options, Willmott says. Sharing this information with patients will help them to manage expectations regarding their treatment journey and empower them through the clinical decisions that are being made, Willmott concludes.

Lyndsay Willmott, MD, discusses the importance of genetic testing in ovarian cancer.

Dr. Willmott on the Importance of Genetic Testing in Ovarian Cancer

Lyndsay Willmott, MD, gynecologic oncologist, Arizona Oncology, discusses selecting among available PARP inhibitors for the treatment of patients with ovarian cancer based on genetic testing results.

Patients whose tumors harbor either a germline or somatic 

 mutation are candidates for treatment with olaparib (Lynparza), according to Willmott. Eligible patients receive 2 years of treatment with olaparib following completion of platinum-based chemotherapy, Willmott explains.

Those with homologous recombination deficiency–positive disease would be best suited for treatment with olaparib plus bevacizumab (Avastin) as first-line maintenance therapy, based on results from the phase 3 PAOLA-1 trial (NCT02477644), Willmott explains. Moreover, data from the phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016) suggest that treatment with niraparib (Zejula) is a feasible option for all patients, regardless of genetic testing results, Willmott notes. 

Due to the variety of available PARP inhibitors in the frontline maintenance setting, genetic testing results can be a valuable tool for guiding treatment decisions, Willmott concludes.

Lyndsay Willmott, MD, discusses selecting among available PARP inhibitors for the treatment of patients with ovarian cancer based on genetic testing results.


Dr. Willmott on Using Genetic Testing to Inform PARP Inhibitor Selection in Ovarian Cancer

Lyndsay J. Willmott, MD, gynecologic oncologist, Arizona Oncology, discusses the mechanisms of resistance to PARP inhibitors that have been identified in ovarian cancer.

Tumor cells in reversion mutations can revert to 

 wild-type and can confer resistance to PARP inhibitors. There can also be upregulation of other types of cell cycle repair such as non-homologous end joining, which is a type of alternative repair in cells that have 

 defaults. Halting the replication fork can also lead to PARP inhibitor resistance.

There can be other acquired types of resistance such as increased efflux of the PARP inhibitor out of the cell, so that it is no longer available for its mechanism of action. PARP inhibitors can sometimes exploit these abnormalities in cell cycle regulation. If you can alter some of these things like cycle independent kinases, that may enable increased PARP activity. There are certainly a number of mechanisms that are being evaluated to see if we can shut down or turn up other systems to allow the inhibitor to remain effective, says Willmott.

Dr. Willmott on Mechanisms of Resistance in Ovarian Cancer

Lyndsay J. Willmott, MD, a gynecologic oncologist with Arizona Oncology, discusses the FDA approval of olaparib (Lynparza) in the maintenance setting for relapsed patients with platinum-sensitive ovarian cancer.

Lyndsay J. Willmott, MD

Articles

Dr. Willmott on Expanding Genomic Testing in Ovarian Cancer

Dr. Willmott on the Importance of Genetic Testing in Ovarian Cancer

Dr. Willmott on Using Genetic Testing to Inform PARP Inhibitor Selection in Ovarian Cancer

Dr. Willmott on Mechanisms of Resistance in Ovarian Cancer

Dr. Willmott on FDA Approval of Maintenance Olaparib in Ovarian Cancer