SGO 2019: Post Hoc Exploratory Analyses From the ARIEL3 Trial in Recurrent Ovarian Cancer
Data from post hoc exploratory analyses from the phase III ARIEL3 clinical study of rucaparib in recurrent ovarian cancer was presented during oral plenary and poster sessions at the Society of Gynecologic Oncology’s (SGO) 50th Annual Meeting on Women’s Cancer. These analyses highlighted ARIEL3 results in different patient demographics, including age and deleterious germline mutation status.
The U.S. Food and Drug Administration approved rucaparib tablets for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who have a complete or partial response to platinum-based chemotherapy in April 2018 based on results from ARIEL3.
Effect of Age on Efficacy and Safety
The efficacy and safety of rucaparib maintenance treatment was investigated in three age-based sub-groups from ARIEL3 in a post hoc exploratory analysis (Abstract 4).
In the intent-to-treat population, investigator-assessed median progression-free survival (PFS) for patients aged < 65 years was 11.1 months (n = 237) in the rucaparib arm vs 5.4 months (n = 117) in the placebo arm (hazard ratio [HR] = 0.33; 95% confidence interval [CI = 0.25–0.43). For patients aged 65–74 years, median PFS was 8.3 months (n = 113) vs 5.3 months (n = 64) (HR = 0.43; 95% CI = 0.29–0.64). For patients aged ≥ 75 years, median PFS was 9.2 months (n = 25) vs 5.5 months (n = 8) (HR = 0.47; 95% CI = 0.16–1.35).
In this dataset, maintenance treatment with rucaparib improved median PFS and reduced the risk of progression vs placebo, regardless of age subgroup. In general, the safety profile of rucaparib was consistent across the three age subgroups.
“As we continue to explore and expand our use of PARP inhibitors for the maintenance treatment of recurrent ovarian cancer, it’s helpful for physicians to know how individual factors such as patient age may impact treatment decisions,” said Jonathan Ledermann, Professor of Medical Oncology, UCL Cancer Institute and UCL Hospitals, London, and global principal investigator for non-U.S. sites in the ARIEL3 study. “In our analysis of the ARIEL3 study, we found that maintenance treatment with rucaparib improved median PFS, reduced the risk of progression, and had a consistent safety profile regardless of age, suggesting that patient age should not discourage physicians from considering rucaparib in this setting.”
Effect of Deleterious Germline BRCA Mutation
In another analysis presented at SGO, researchers assessed PFS in a subgroup of patients with a deleterious germline BRCA mutation and in patients without a deleterious germline BRCA mutation (Poster 2402).
In these subgroups, rucaparib significantly improved PFS vs placebo, regardless of BRCA mutation status. Although the reduction in risk was numerically greater in the germline BRCA mutation subgroup (HR = 0.25; 95% CI = 0.16–0.39) than in the no germline BRCA mutation subgroup (HR = 0.41; 95% CI = 0.32–0.52), the reduction in risk between the two subgroups did not differ by a statistically significant margin. The safety profile of rucaparib vs placebo in the germline BRCA mutation and no germline BRCA mutation subgroups was consistent with the safety profile of rucaparib in the overall safety population reported previously.
This post hoc exploratory analysis demonstrated that the reduction in risk was numerically greater in the germline BRCA mutation subgroup than in the no germline BRCA mutation subgroup. In the no germline BRCA mutation subgroup, the observed improvement in PFS was not driven solely by the somatic BRCA mutation/wild-type BRCA/high loss of heterozygosity subgroup as demonstrated by the analysis of patients with wild-type BRCA tumors.
“While it is evident that women whose tumors possess a BRCA mutation derive the greatest benefit from rucaparib therapy, the data presented in this poster demonstrate the meaningful and clinically relevant benefit that eligible patients, including those without a BRCA mutation, may receive as a result of maintenance treatment,” said Robert L. Coleman, MD, Professor, Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center in Houston and co-coordinating investigator in the ARIEL3 clinical trial program. “These data further reinforce the importance of maintenance treatment for women with recurrent ovarian cancer vs the previous standard of observation following treatment with chemotherapy.”
Disclosure: The study authors' full disclosures can be found at sgo.confex.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
