Richard T. Penson, MD, MRCP, clinical director, Medical Gynecologic Oncology, Medicine, Massachusetts General Hospital, associate professor of medicine, Harvard Medical School, discusses selecting between PARP inhibitors for switch maintenance therapy in recurrent ovarian cancer.

Currently, 3 PARP inhibitors are FDA approved as switch maintenance therapy options for patients with platinum-sensitive recurrent ovarian cancer who had a complete or partial response to platinum-based therapy, Penson says. These agents include olaparib (Lynparza), niraparib (Zejula), and rucaparib (Rubraca) and all have demonstrated similar efficacy in this patient population.

Regarding safety, the 3 agents also have similar safety profiles, assuming the 200-mg dose of niraparib is utilized, Penson explains. Common adverse effects include nausea and fatigue. Additionally, patients must be informed about the small risk for myelodysplastic syndrome and acute myeloid leukemia with PARP inhibitors.

Ultimately, switch maintenance therapy with PARP inhibitors improves outcomes for patients with recurrent ovarian cancer and is a standard treatment option, Penson concludes.

Videos

Richard T. Penson, MD, MRCP, discusses selecting between PARP inhibitors for switch maintenance therapy in recurrent ovarian cancer.  



Dr. Penson on PARP Inhibitors as Switch Maintenance Therapy in Recurrent Ovarian Cancer 

Richard T. Penson, MD, MRCP, associate professor of medicine, Harvard Medical School, and clinical director of Medical Gynecologic Oncology, in the Department of Medicine, Massachusetts General Hospital, discusses re-challenging with PARP inhibition in patients with ovarian cancer.

Patients who progress on PARP inhibition should not be immediately re-challenged with another PARP inhibitor, says Penson. However, patients who receive PARP inhibition in the adjuvant setting followed by a 6-month platinum-sensitive interval may be able to be re-challenged with a PARP inhibitor.

Although such as an approach has yet to be validated, data from a small, retrospective study presented at the 2019 SGO Annual Meeting showed that prior exposure to a PARP inhibitor does not prevent patients from responding to another PARP inhibitor in later lines of therapy. The results showed encouraging responses in patients who received a second PARP inhibitor, including a 13.6% partial response rate and a 59.1% stable disease rate.

Dr. Penson on Re-Challenging With PARP Inhibition in Ovarian Cancer

Richard T. Penson, MD, MRCP, associate professor of medicine, Harvard Medical School, and clinical director of Medical Gynecologic Oncology, in the Department of Medicine, Massachusetts General Hospital, discusses unexpected findings from the phase III SOLO3 trial and ongoing research with PARP inhibitors in ovarian cancer.

Olaparib (Lynparza) led to a higher objective response rate versus chemotherapy in patients with platinum-sensitive, relapsed, germline 

-mutant ovarian cancer who received ≥2 prior lines of chemotherapy, according to data from the phase III SOLO3 trial. Pneumonitis, one of the adverse events of special interest, was not reported in any patients on trial, says Penson.

Now that PARP inhibitors have shown therapeutic benefit in the frontline maintenance and recurrent settings, investigators are evaluating re-exposure to PARP therapy. For example, in the phase IIIb OReO trial, patients with platinum-sensitive disease with a PARP-free interval ≥6 months will be randomized to maintenance therapy with either olaparib or placebo. The results of the study will shed light on the benefit of re-challenging patients with a PARP inhibitor and potential biomarkers of response, concludes Penson.

Richard T. Penson, MD, MRCP, discusses unexpected findings from the phase III SOLO3 trial and ongoing research with PARP inhibitors in ovarian cancer.

Dr. Penson on Research With PARP Inhibitors in Ovarian Cancer

Richard T. Penson, MD, MRCP, associate professor of medicine, Harvard Medical School, and clinical director of Medical Gynecologic Oncology, in the Department of Medicine, Massachusetts General Hospital, discusses the eligibility criteria for PARP inhibitors in advanced ovarian cancer.

Historically, platinum-sensitivity has been used to predict for response to PARP inhibition, says Penson. Now, the histology, genetic markers, and the treatment-free interval are all taken into consideration. Notably, patients with clear cell or mucinous tumors are more likely to benefit from bevacizumab (Avastin) than they are from a PARP inhibitor.

Additionally, CA-125 levels can help determine the magnitude of benefit patients will experience from a PARP inhibitor, says Penson. In patients who get a rapid response to platinum-based therapy in the recurrent setting, Penson recommends giving 4 cycles of platinum-based therapy and switching to a PARP inhibitor early on to reduce toxicity and jumpstart treatment that's going to have a larger impact in terms of the duration of disease control.

Dr. Penson on the Eligibility Criteria for PARP Inhibitors in Advanced Ovarian Cancer

Richard T. Penson, MD, MRCP, associate professor, Harvard Medical School, and clinical director, Medical Gynecologic Oncology, Medicine, Massachusetts General Hospital, discusses prospective biomarkers that may predict response to PARP inhibitors in advanced ovarian cancer.

 mutations are somatic, says Penson. Because somatic mutations are not inherited, they are not as commonly tested for. However, there has been a steady uptick of tissue tests in addition to germline testing in the blood or saliva, adds Penson.

About half of high-grade serious endometrioid tumors harbor homologous recombination deficiency (HRD) which is another important marker to look for.

Lastly, the field is evaluating a new generation of assays that will identify optimal combination therapies, says Penson. Approximately 20% to 30% of patients who harbor a 

 mutation will acquire a reversion mutation. As such, assays that can help determine a combination that has the potential to overcome this resistance will be important, concludes Penson.

Richard T. Penson, MD, MRCP

Articles

Dr. Penson on PARP Inhibitors as Switch Maintenance Therapy in Recurrent Ovarian Cancer

Dr. Penson on Re-Challenging With PARP Inhibition in Ovarian Cancer

Dr. Penson on Research With PARP Inhibitors in Ovarian Cancer

Dr. Penson on the Eligibility Criteria for PARP Inhibitors in Advanced Ovarian Cancer

Dr. Penson on Biomarkers of Response to PARP Inhibitors in Ovarian Cancer