Casey M. Cosgrove, MD, gynecologic oncologist, member, Translational Therapeutics Program, The Ohio State University Comprehensive Cancer Center–James, assistant professor, Department of Gynecologic Oncology, The Ohio State University College of Medicine, discusses utilizing biomarker-informed treatments in endometrial cancer.

Historically, treatment selection has been guided by histology and other disease features, Cosgrove says. Now however, it is possible to utilize molecular signatures to determine whether the cancers are at a high- or low-risk of recurrence, Cosgrove explains. Moreover, research suggest that certain markers can predict for higher-risk cancers, including markers such as 

 mutations and genomic alterations, Cosgrove adds.

Patients with high-risk features may benefit from extra treatment, Cosgrove continues. Moreover, the biomarker 

is needed to help the DNA repair itself, Cosgrove explains. The presence of a 

 mutation allows a patient’s immune system, without any additional treatment, to fight cancer cells more efficiently, making these patients areless likely to recur, Cosgrove says.

A question that has been asked among groups is whether treating these patients can be forgone, even if they traditionally would have had higher-risk features, Cosgrove concludes.

Videos

Casey M. Cosgrove, MD, discusses utilizing biomarker-informed treatments in endometrial cancer. 


Dr. Cosgrove on Utilizing Biomarker-Informed Treatments Endometrial Cancer 

Casey M. Cosgrove, MD, gynecologic oncologist, The Ohio State University Comprehensive Cancer Center—The James, and assistant professor, Department of Gynecologic Oncology, The Ohio State University College of Medicine, discusses the utilization of PARP inhibition in ovarian cancer.

PARP inhibition in platinum-sensitive ovarian cancer is used in 2 main settings: maintenance and treatment. When using PARP inhibitors as maintenance therapy, patients recur, receive platinum-based chemotherapy again, achieve a complete or partial response, and then go on to receive a PARP inhibitor as a maintenance therapy. Olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula) are all FDA approved for use as maintenance therapy in patients with ovarian cancer, says Cosgrove. Since it is difficult to compare the 3 PARP inhibitors, choosing among them is based on provider preference and safety profiles, adds Cosgrove.

PARP inhibitors are also being used in platinum-sensitive ovarian cancer as treatment. Olaparib, rucaparib, and niraparib are also approved for use in the treatment setting for this patient population, albeit for different indications, with 

niraparib most recently getting FDA approval

 in October 2019. When determining which PARP inhibitor to give a patient with ovarian cancer, providers mostly rely on the presence of some sort of biomarker, including the presence of 

mutations or homologous recombination deficiency, concludes Cosgrove.

Articles

Casey M. Cosgrove, MD, discusses the utilization of PARP inhibition in ovarian cancer.

Dr. Cosgrove on the Utilization of PARP Inhibition in Ovarian Cancer

Casey M. Cosgrove, MD, gynecologic oncologist, The Ohio State University Comprehensive Cancer Center—James, and assistant professor, Department of Gynecologic Oncology, The Ohio State University College of Medicine, discusses the approval of niraparib (Zejula) in advanced ovarian cancer.

In October 2019, niraparib was granted FDA approval for the treatment of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with ≥3 prior chemotherapy regimens, and whose cancer is associated with homologous recombination deficiency (HRD)—positive status.

The approval was based on the single-arm, phase II QUADRA trial which showed an overall response rate (ORR) of 24% with niraparib monotherapy (95% CI, 16-34). Moreover, patients with platinum-sensitive, 

-mutant ovarian cancer had an ORR of 39% (95% CI, 17-64) compared with 29% (95% CI, 11-52) and 19% (95% CI, 4-46) in those with platinum-resistant disease and platinum-refractory disease, respectively.

HRD has been shown to be a predictive biomarker for response to PARP inhibitors in this space, concludes Cosgrove.

Casey M. Cosgrove, MD, discusses the approval of niraparib in advanced ovarian cancer.

Dr. Cosgrove on the Approval of Niraparib in Advanced Ovarian Cancer

Casey M. Cosgrove, MD, gynecologic oncologist, The Ohio State University Comprehensive Cancer Center—James, and assistant professor, Department of Gynecologic Oncology, The Ohio State University College of Medicine, discusses retreatment with PARP inhibitors in recurrent ovarian cancer.

A data gap exists when it comes to treating patients who have already received a PARP inhibitor, says Cosgrove. With the SOLO-1 data, and now the PRIMA data, more patients are going to receive PARP inhibitors up front as part of their maintenance treatment after primary therapy, he adds. However, there are no robust data to suggest that retreatment with a different PARP inhibitor would be effective.

The question of retreatment is being evaluated in the phase IIIb OReO trial (NCT03106987). In this trial, patients who receive chemotherapy followed by maintenance PARP inhibition and recur will receive platinum-based chemotherapy and be randomized to either olaparib (Lynparza) or placebo. The study will shed light on whether using a PARP inhibitor after another PARP inhibitor is a viable strategy, concludes Cosgrove.

Casey M. Cosgrove, MD, gynecologic oncologist, The Ohio State University Comprehensive Cancer Center–James, and assistant professor, Department of Gynecologic Oncology, The Ohio State University College of Medicine, discusses retreatment with PARP inhibitors in recurrent ovarian cancer.

Dr. Cosgrove on Retreatment With PARP Inhibitors in Ovarian Cancer

Casey M. Cosgrove, MD, gynecologic oncologist, assistant professor, Department of Gynecologic Oncology, The Ohio State University Comprehensive Cancer Center, discusses factors to consider when selecting a PARP inhibitor as maintenance therapy in advanced ovarian cancer.

Currently, olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula) are FDA approved as maintenance therapy in women with recurrent ovarian cancer who have achieved a partial or complete response to platinum-based chemotherapy, explains Cosgrove. 

Some PARP inhibitors are more likely to cause bone marrow suppression or gastrointestinal adverse events (AEs). As such, the toxicity profiles of these agents should factor into treatment selection, so as to mitigate these AEs. As each agent has demonstrated similar efficacy in this space, patient preference should also factor into the decision, concludes Cosgrove. 

Casey M. Cosgrove, MD, discusses factors to consider when selecting a PARP inhibitor as maintenance therapy in advanced ovarian cancer.
 

Casey M. Cosgrove, MD

Articles

Dr. Cosgrove on Utilizing Biomarker-Informed Treatments Endometrial Cancer

Dr. Cosgrove on the Utilization of PARP Inhibition in Ovarian Cancer

Dr. Cosgrove on the Approval of Niraparib in Advanced Ovarian Cancer

Dr. Cosgrove on Retreatment With PARP Inhibitors in Ovarian Cancer

Dr. Cosgrove on Selecting a PARP Inhibitor for Maintenance Therapy in Ovarian Cancer