Rucaparib (Rubraca) significantly improved progression-free survival when administered as maintenance treatment in newly diagnosed patients with advanced ovarian cancer.
Results from the phase 3 ATHENA trial show that rucaparib (Rubraca) significantly improved investigator-assessed progression-free survival (PFS) compared with placebo when administered as maintenance treatment in newly diagnosed patients with advanced ovarian cancer after successful first-line treatment with platinum-based chemotherapy.1
In the homologous recombination deficiency (HRD)–positive population of the phase 3 ATHENA trial (GOG 3020/ENGOT-ov45; NCT03522246; ATHENA-MONO), rucaparib (n = 185) achieved statistical significance versus placebo (n = 49) in the primary end point of PFS, with a hazard ratio (HR) of 0.47 (95% CI, 0.31-0.72). Median PFS in the investigative and control cohorts was 28.7 months and 11.3 months, respectively (P = .0004).
“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,” Bradley J. Monk, MD, FACOG, FACS, at GOG Foundation, HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, said in a press release. “The results of ATHENA-MONO address many of these unanswered questions and expands the opportunity for rucaparib for all patients regardless of biomarker status.”
ATHENA, a double-blind, placebo-controlled, phase 3 trial, is comprised of the ATHENA-MONO and ATHENA-COMBO portions. To be eligible for enrollment in the trial, patients needed to be at least 18 years of age with newly diagnosed, advanced, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer, and have achieved a response after completing cytoreductive surgery and frontline platinum-based chemotherapy.2 Patients could not have been previously administered treatment for their disease other than first-line platinum treatment.
In the intention-to-treat (ITT) patient population (n = 538), which included all patients randomized in the trial, median PFS with rucaparib (n = 427) was 20.2 months compared with 9.2 months with placebo (n = 111). This finding was deemed statistically significant (HR, 0.52; 95% CI, 0.40-0.68; P < .0001).
Patients in the study were randomized 4:4:1:1 to oral rucaparib plus intravenous (IV) nivolumab (nivolumab; arm A); oral rucaparib plus IV placebo (arm B); oral placebo plus IV nivolumab (arm C); and oral placebo plus IV placebo (arm D). Treatment with rucaparib was initiated at a starting dose of 600 mg twice daily, whereas nivolumab was initiated at a dose of 480 mg every 4 weeks.
The ATHENA-MONO portion of the trial evaluated arm B versus arm D to analyze single-agent rucaparib compared with placebo in these patient populations. The ATHENA-COMBO group is evaluating arm A versus arm B of the trial to analyze the efficacy of rucaparib/nivolumab compared with single-agent rucaparib in this population.
The primary end point of the trial was investigator-assessed PFS per RECIST v1.1 criteria.
ATHENA-MONO included 538 patients with a primary efficacy analysis of 2 prospectively-defined molecular subsets in a step-down manner of patients who are HRD-positive, including BRCA-mutated tumors, as well as in the ITT population. In the exploratory HRD-negative subgroup, the study showed that median PFS with rucaparib (n = 189) was 12.1 months compared with 9.1 months in the placebo group (n = 49; HR, 0.65; 95% CI, 0.45-0.95; P = .0284).
An analysis of an additional subgroup of patients with BRCA-mutated tumors found that median PFS with rucaparib (n = 91) was not yet reached per investigator assessment compared with 14.7 months with placebo (n = 24), with an HR of 0.40 (95% CI, 0.21-0.75; P = .0041).
The most frequent grade 3 or higher treatment-emergent adverse events (AEs) with rucaparib in ATHENA-MONO were anemia/decreased hemoglobin (28.7%), neutropenia (14.6%), elevated alanine/aspartate aminotransferase (10.6%), and thrombocytopenia (7.1%). Treatment-emergent myelodysplastic syndrome/acute myeloid leukemia was found in 0.2% of patients administered rucaparib compared with 0% of patients administered placebo.
Treatment-emergent AEs resulted in discontinuation for 11.8% of patients administered rucaparib and 5.5% of individuals in the placebo group.
“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 and lead ENGOT/NCRI National Cancer Research Institute investigator of ATHENA, said in a press release.
“The ATHENA-MONO study demonstrates the role of rucaparib monotherapy in the first-line maintenance treatment setting for advanced ovarian cancer.”
Clovis Oncology, Inc has subsequently announced plans to submit a supplement new drug application to the FDA for approval of rucaparib in this patient population in the second quarter of 2022.