Tricky But Treatable
Pembrolizumab alone and with olaparib offer winning combination in treatment of advanced ovarian cancer.
Pembrolizumab, the immunologic drug already known for its efficacy in treating a host of cancers, is shaping up to be an equally powerful tool in the fight against advanced, BRCA1 and 2-nonmutated epithelial ovarian cancer (EOC), when paired with chemotherapy.
This winning, first-line, treatment combination was the focus of the new study presented earlier today, “Chemotherapy with or without pembrolizumab followed by maintenance with olaparib or placebo for first-line treatment of advanced BRCA non-mutated epithelial ovarian cancer: results from the randomized phase 3 ENGOTOV43/GOG-3036/KEYLYNK-001 study.”
The aim of achieving progression-free survival (PFS) was significant when the two were given together versus chemotherapy alone. Specifically, there was a 47% improvement in PFS and 39% improvement in overall survival (OS) with the combined regimen in the patients that benefited most.
“The tricky thing about ovarian cancer is that there are a lot of different predictors about how people are going to do. It depends on many factors, including the specific cell type of ovarian cancer a patient has, how surgery went, whether they had chemo first, followed by surgery, followed by more chemo, etc.,” said the study’s primary investigator Matthew A. Powell, MD, a professor of gynecologic oncology at Washington University in St. Louis. “So, when you have a study of this size, it allows us to really home in on which group can benefit. The important news is that the results showed a 47% improvement in PFS in the high-grade population that did not receive bevacizumab with a strong marker of pembrolizumab efficacy (combined positive score (CPS) greater than or equal to 10). This means we kept the disease away longer or kept them from dying longer when we simply add pembrolizumab to their standard chemotherapy and continue it after the chemotherapy has completed.”
The study included a cohort of 1,367 patients with newly diagnosed, BRCA1 and 2-nonmutated, stage 3 or 4 EOC, primary peritoneal cancer, or fallopian tube cancer. Patients were randomized into three groups—pembrolizumab plus chemotherapy (paclitaxel-carboplatin) followed by pembrolizumab plus olaparib maintenance; pembrolizumab plus chemotherapy followed by pembrolizumab plus placebo maintenance; and placebo plus chemotherapy followed by placebo maintenance.
According to Dr. Powell, the study allowed for the use of the monoclonal antibody drug, bevacizumab during chemotherapy and maintenance, and just under half chose this approach. Patients received pembrolizumab 200mg Q3W for 35 cycles, chemotherapy for five cycles, and maintenance olaparib therapy 300mg twice daily for up to two years. The primary endpoint was PFS, while the secondary endpoint was overall survival (OS).
Researchers observed PFS benefit with pembrolizumab-olaparib at both the interim and final analysis (median follow-up, 39.8 months), Dr. Powell said. However, the significance threshold of pembrolizumab versus control in the CPS greater than 10 population was not met. As such, formal testing of PFS in the overall population and OS was not performed.
The study’s authors also noted that safety was consistent with the known safety profiles of each agent. Treatment-related adverse event rates were 65.7% in the pembrolizumab-olaparib group, 55.9% in the pembrolizumab group, and 51.1% in the control group.
“Standard treatment for what we call ovarian cancer has been carboplatin and paclitaxel for about 30 years,” Dr. Powell said. “So, this study, which includes data from 224 sites across the globe (22 countries), is very exciting for this patient population and offers hope for improved outcomes.”
Dr. Powell noted that there are 15 different cancers currently benefitting from the use of pembrolizumab because it is so effective across multiple tumor types.
“Two years ago, we basically changed the standard endometrial cancer, a form of uterine cancer, with the addition of pembrolizumab, dramatically keeping the disease away longer, but most importantly having patients live longer,” he said. “I think this could end up being the standard care for patients with certain types of advanced ovarian cancer.”
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