Treatment with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib prior to surgical intervention and chemotherapy has demonstrated the potential for favorable surgical options, manageable adverse events, and positive health outcomes in patients with ovarian cancer who have a germline mutation, according to findings presented by Westin et al at the Society of Gynecologic Oncology 2023 Annual Meeting on Women’s Cancer. The findings demonstrated that neoadjuvant olaparib may be feasible, with 100% of trial participants able to receive both cycles and a 100% rate of optimal tumor reduction among the 93% trial participants who were able to undergo subsequent surgery.
Background
Historically, PARP inhibitors have followed cytotoxic chemotherapy as a maintenance medication—often taken long-term among patients with ovarian cancer.
“Patients are interested in receiving therapies specifically targeting their tumor,” emphasized Shannon N. Westin, MD, MPH, FACOG, Professor and Clinical Medical Director of Gynecologic Oncology and Reproductive Medicine in the Division of Surgery, and Co-Director of the Ovarian Cancer Moonshot Program at The University of Texas MD Anderson Cancer Center, Houston. “There was great excitement among patients for the opportunity to not receive chemotherapy.”
Study Methods and Results
In the new single-arm, open-label Neoadjuvant Olaparib Window (NOW) trial (ClinicalTrials.gov identifier NCT03943173), the researchers involved 15 patients with advanced-stage, high-grade epithelial ovarian cancer, peritoneal cancer, or fallopian tube carcinoma—all of whom had a germline mutation in BRCA1, BRCA2, RAD51C, or PALB2. About 40% of the patients had stage IV disease. Among patients treated first with two cycles of neoadjuvant olaparib—followed by surgery and adjuvant chemotherapy—85% of them were disease free at the completion of all therapies.
Patients experienced expected adverse events such as abdominal pain, constipation, anemia, nausea, and pain during olaparib treatment. The researchers noted that the only severe adverse event reported was grade 3 anemia in three patients.
Conclusions
The researchers hope their findings will help justify further research to determine whether PARP inhibitors can be given in lieu of chemotherapy in the neoadjuvant setting.
“This study provides a potential template for how we might vet targeted therapies earlier in the treatment continuum,” Dr. Westin said. “As drug options increase, it is encouraging to see opportunities for patients to get tested at diagnosis and receive targeted therapy in lieu of or in addition to chemotherapy,” she concluded.
