Jinan Liu, MD, PhD, Director of Oncology, Value, Evidence and Outcomes, GlaxoSmithKline (GSK), discusses results from a real-world study exploring patterns and predictors of maintenance therapy use among patients with newly diagnosed ovarian cancer.     

This study was presented at the virtual 2021 ASCO Annual Meeting.

Transcript:

My name is Jinan Liu. I'm a director of Value Evidence and Outcomes at GlaxoSmithKline. I'm excited to share a summary of two abstracts from Dr Chan of Sutter Health in San Francisco, Dr Thaker of Washington University School of Medicine in St. Louis, and my colleagues at GSK, that were e-published as part of 2021 American Society of Clinical Oncology annual meeting.

Ovarian cancer remains a leading cause of death among gynecologic cancers. Most of the patients experience disease recurrence despite initial responsiveness to first-line treatment. To delay recurrence, maintenance therapies have been introduced in patients who respond to first-line treatment.

Options for first-line maintenance therapy have evolved in the US in recent years, particularly with the FDA approvals of PARP inhibitors.

Olaparib was approved in 2018 for first-line maintenance treatment of patients with advanced ovarian cancer with the BRCA mutation, and in 2020 as combination therapy with bevacizumab for first-line maintenance treatment of patients with homologous recombination-deficient tumors.

Additionally, the FDA approved niraparib in 2020 for maintenance treatment of patients with advanced ovarian cancer, regardless of tumor biomarker status.

To better understand how first-line maintenance therapy is used in clinical practice, we use the Flatiron Health database to retrospectively evaluate the use and outcomes of first-line maintenance therapy in patients with ovarian cancer treated in a real-world setting prior to the most recent 2020 FDA approvals.

The Flatiron Health database is longitudinal-electronic-health-record-derived database that consists of de-identified patient-level data that are curated via technology-enabled abstractions.

In our analysis, we focused on patients with newly-diagnosed stage 3 or 4 ovarian cancer who are treated with six to nine cycles of first-line platinum-based chemotherapy, and received either primary debulking surgery or interval debulking surgery following new adjuvant chemotherapy between January 1st, 2016 and February 29th, 2020.

The end of the last cycle of first-line platinum-based chemotherapy was defined as the index state to focus solely on patients who responded to first-line treatment and would be considered eligible for PARP inhibitors therapy. Patients who started the second-line treatment within two months of the index state were excluded.

On selection, patients were classified into two cohorts: patients who were treated with first-line maintenance therapy and those who were treated with active surveillance.

Logistic regression analysis was used to identify variables predictive of first-line maintenance therapy use and a time to initiation of a second-line systemic therapy or death was used as a surrogate to assess time to disease progression.

Inverse probability of treatment waiting and our Cox proportional-hazards model were used to adjust for baseline differences across the two cohorts. 463 patients were included in the analysis. 87.7% of the patients were treated in community practices, and 12.3% were treated in academic institutions.

Overall, 21% of patients received maintenance therapy versus 79% received active surveillance. In patients who received the maintenance therapy, 48.5% received bevacizumab, 40.2% received a PARP inhibitor, and 11.3% received paclitaxel.

Patients with BRCA wild-type were significantly less likely to receive maintenance therapy than patients with BRCA mutations. Hazard ratio, 0.30. Patients treated in 2018 and 2019 were significantly more likely to receive maintenance therapy than patients treated in 2017. Hazard ratio of 2.73 and 8.78 respectively.

Age, race, practice type, ECOG score, and residual disease status were not significant predictors of first-line maintenance therapy use. Median progression-free survival or PFS for patients who received the first-line maintenance therapy was 16.1 months, compared with 12.2 months in patients treated with active surveillance.

After adjusting for baseline differences in characteristics and demographics, including age, race, stage of cancer, and the BRCA status, patients who received the first-line maintenance therapy had a statistically significant, 29%, lower risk of progression or death than those who treated with active surveillance (Hazard ratio, 0.71; P = .04).

In this real-world analysis, the majority of patients with newly-diagnosed advanced ovarian cancer did not receive first-line maintenance therapy. Predictors of first-line maintenance therapy use were BRCA mutation status and year of treatment, with maintenance therapy use increasing over time.

Despite the lower utilization of first-line maintenance therapy, a significant progression-free survival benefit was found in those receiving maintenance therapy compared with those receiving active surveillance.

Further studies are needed to understand how biomarker status drives practice patterns, and how to adjust barriers to the appropriate use of maintenance therapy in patients with advanced ovarian cancer.

Thank you for your time.