FDA Approval Insights: Olaparib/Bevacizumab in HRD+ Advanced Ovarian Cancer

Welcome to a very special edition of OncLive^® On Air! I’m your host today, Jessica Hergert.

OncLive^® On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

Today, we had the pleasure of speaking with Thomas Herzog, MD, deputy director of the University of Cincinnati Cancer Institute and a professor of Obstetrics and Gynecology at the UC College of Medicine, to discuss the FDA approval of the combination of olaparib (Lynparza) and bevacizumab (Avastin) as a frontline maintenance therapy for patients with advanced ovarian cancer.

On May 8, 2020, the FDA approved the combination of olaparib and bevacizumab for the maintenance treatment of patients with advanced ovarian cancer who are in complete or partial response (PR) to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)—positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability.

The approval is based on findings from the pivotal phase 3 PAOLA-1 trial, in which the combination reduced the risk of disease progression or death compared with bevacizumab alone.

The benefit with the addition of olaparib was most pronounced in patients with HRD-positive tumors, including tumors that had BRCA mutations. In this subgroup, the median progression-free survival (PFS) was 37.2 months and 17.7 months with the olaparib combination and bevacizumab alone, respectively.

In those who had HRD-positive tumors without BRCA mutations, the median PFS was 28.1 months with olaparib/bevacizumab and 16.6 months with bevacizumab alone. In the intent-to-treat population, the combination led to a 41% reduction in the risk of disease progression or death compared with bevacizumab alone per investigator assessment. Additionally, after a median follow-up of 22.9 months, the median PFS was 22.1 months and 16.6 months with the combination and bevacizumab alone, respectively.

Regarding safety, the most common adverse events (AEs) occurring in at least 20% of patients in the combination arm versus the bevacizumab-alone arm included fatigue, nausea, hypertension, anemia, lymphopenia, vomiting, and arthralgia. Grade 3 or greater AEs were reported in 57% of patients who received the addition of olaparib to bevacizumab and occurred in 51% of patients on bevacizumab alone. These AEs included hypertension, anemia, lymphopenia, fatigue, neutropenia, nausea, diarrhea, leukopenia, vomiting, and abdominal pain.

The approval of olaparib and bevacizumab indicates that patients’ eligibility for therapy must be established by an FDA-approved companion diagnostic for olaparib. As such, on May 11, 2020, the FDA approved myChoiceCDx for use as a companion diagnostic to identify patients with advanced ovarian cancer with positive HRD status.

Olaparib is also approved as maintenance monotherapy for patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or PR to frontline platinum-based chemotherapy based on data from the phase 3 SOLO-1 trial.

In our exclusive interview, Dr. Herzog shed light on key findings from the PAOLA-1 trial, the implications of the approval of the combination for patients with advanced ovarian cancer, and ongoing research with olaparib.