Rucaparib Improves PFS in Advanced Ovarian Cancer

The PARP inhibitor rucaparib significantly prolonged progression-free survival compared with placebo as a first-line maintenance treatment in previously treated patients with ovarian cancer.

First-line maintenance treatment with rucaparib (Rubraca) significantly improved progression-free survival (PFS) among patients with advanced ovarian cancer who had prior platinum-base chemotherapy, meeting the primary end point of the ATHENA-MONO study (NCT03522246).1

Among the 538 patients randomized to receive rucaparib, the median PFS was 20.2 months with rucaparib compared with 9.2 months with placebo (HR, 0.52; 95% CI, 0.40-0.68; P <.0001) in the intent-to-treat population, according to an investigator review.

Similarly, in a homologous recombination deficiency [HRD]-positive population, the median PFS was 28.7 months with rucaparib compared with 11.3 months with placebo (HR, 0.47; 95% CI, 0.31-0.72; P = .0004). Furthermore, in the HRD-negative population, the PARP inhibitor yielded a median PFS of 12.1 months vs 9.1 months with placebo (HR, 0.65; 95% CI, 0.45-0.95; P = .0284).

Positive results were also observed in the exploratory BRCA-mutant subgroup. In this population, the median PFS was not reached (NR) vs 14.7 months for those who received placebo (HR, 0.40; 95% CI, 0.21-0.75; P = .0041). These results were consistent among those with germline BRCA and somatic BRCA mutations, as well.

“I believe the significant improvement in PFS demonstrated in the ATHENA-MONO trial underscores the importance of first-line maintenance therapy and the benefit that rucaparib can provide to women with advanced ovarian cancer irrespective of HRD status,” Rebecca S. Kristeleit, MD, PhD, of Guy’s and St Thomas’ NHS Foundation Trust in London and lead ENGOT/NCRI National Cancer Research Institute investigator of the ATHENA trial, said in a news release.

“Ovarian cancer remains a leading cause of cancer-related death among women, which highlights the continued need for new treatment options and strategies for women with newly diagnosed disease. The ATHENA-MONO study demonstrates the role of rucaparib monotherapy in the first-line maintenance treatment setting for advanced ovarian cancer.”

The double-blind, placebo-controlled, phase 3 ATHENA trial sought to evaluate rucaparib as a first-line ovarian maintenance treatment in patients with high-grade ovarian, fallopian tube, or primary peritoneal cancer.2 In the ATHENA-MONO arm of the study, which pits the PARP inhibitor as a monotherapy against placebo, 538 women were enrolled. The ATHENA-COMBO arm, which is set to compare rucaparib/nivolumab with single-agent rucaparib, is expected to have results by 2023.

The trial did not yield any new safety signals in regard to previously reported adverse events (AEs). The most common 3/4 treatment-emergent AEs (TEAEs) included anemia/decreased hemoglobin (28.7%), neutropenia (14.6%), alanine aminotransferase and raised aspartate aminotransferase increase (10.6%), and thrombocytopenia (7.1%). Overall, 11.8% of patients receiving rucaparib needed to discontinue treatment because of TEAEs compared with 5.5% of patients receiving placebo.

In the experimental arm, 0.2% of patients experienced treatment-emergent myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML). No patients on the placebo arm experienced this TEAE.

“While PARP inhibitors have shown efficacy as first-line maintenance treatment for patients with advanced ovarian cancer, questions still remain about the patient population that may benefit from their use. The results of ATHENA-MONO address many of these unanswered questions and expands the opportunity for rucaparib in all patients regardless of biomarker status,” added Bradley J. Monk, MD, FACOG, FACS, at GOG Foundation, HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ and global primary investigator of the ATHENA trial.

Additional analyses from the ATHENA-MONO will be presented at the 2022 ASCO Annual Meeting.

Reference

  1. Clovis Oncology’s Rubraca (rucaparib) significantly improves progression-free survival in first-line maintenance treatment in women with ovarian cancer regardless of their biomarker status in phase 3 ATHENA-MONO trial. Clovis Oncology. March 31, 2022. Accessed March 31, 2022. https://bit.ly/3K0hAP9
  2. Monk BJ, Coleman RL, Fujiwara K, et al. ATHENA (GOG-3020/ENGOT-ov45): a randomized, phase III trial to evaluate rucaparib as monotherapy (ATHENA-MONO) and rucaparib in combination with nivolumab (ATHENA-COMBO) as maintenance treatment following frontline platinum-based chemotherapy in ovarian cancer. Int J Gynecol Cancer. 2021;31(12):1589-1594. doi:10.1136/ijgc-2021-002933