A significant improvement in progression-free survival was observed in the phase 3 ATHENA-MONO trial with first-line maintenance rucaparib vs placebo in patients with advanced ovarian cancer.
Progression-free survival (PFS) was significantly improved with first-line rucaparib (Rubraca) as a maintenance monotherapy compared with a placebo for patients with advanced ovarian cancer following treatment of platinum-based chemotherapy regardless biomarker status, according to results from the phase 3 ATHENA-MONO trial (NCT03522246).
The median PFS was 20.2 months in the rucaparib group and 9.2 months in the placebo group in the intent-to-treat population (HR, 0.47; 95% CI, 0.31-0.72; P <.0001). Those in the HRD-positive subgroup had a median PFS of 28.7 months vs 11.3 months in the placebo group (P = .0004).
The drug’s developer, Clovis Oncology, noted that these results will be used to support a supplement new drug application the label expansion of which is expected to be submitted during Q2 2022. Data from the trial have been submitted for presentation at the 2022 American Society of Clinical Oncology Annual Meeting.
“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,” primary investigator Bradley J. Monk, MD, FACOG, FACS, professor in the Division of Gynecologic Oncology at Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine at St. Joseph’s Hospital, as well as the medical director of the Gynecologic Program at US Oncology Research, said in a press release.
In addition to the ATHENA-MONO trial, the ATHENA-COMBO trial will assess the use of rucaparib plus nivolumab (Opdivo) vs rucaparib, the results of which are expected to read out in Q1 2023 due to slower than expected event count.
The ATHENA-MONO trial enrolled 538 patients with high-grade ovarian, fallopian tube, or primary peritoneal cancer. The trial included 2 prospectively defined molecular sub groups including patients who were HRD-positive—including of BRCA-mutant tumors—and all patients in the randomized ITT group. A total of 185 patients were included in the rucaparib arm and 49 were in the placebo arm.
Additional findings from the study indicated that statistical significance was reached in all 538 patients who received rucaparib. When assessed by investigator review, 427 patients in the rucaparib arm achieved significance compared with 111 in the placebo arm for the primary end point (HR, 0.52; 95% CI, 0.40-0.68).
By investigator review, the HRD-negative subgroup had a median PFS was 12.1 months in the rucaparib group and 9.1 months in the placebo group (HR, 0.65; 95% CI, 0.45-0.95; P = .0284).
Those with a BRCA mutation had a median PFS that was not reached in the rucaparib group vs 14.7 months in the placebo group (HR, 0.40; 95% CI, 0.21-0.75; P = .0041). Results were consistent for those with a germline BRCA mutation, somatic BRCA mutation, and unknown populations.
Grade 3/4 treatment-emergent adverse effects (TEAEs) seen in patients included anemia (28.7%), neutropenia (14.6%), alanine aminotransferase increase/aspartate aminotransferase increase (10.6%), and thrombocytopenia (7.1%). In total, 11.8% of patients in the rucaparib arm and 5.5% in the placebo arm discontinued treatment because of TEAEs.
“The results from the ATHENA-MONO study of [rucaparib] in first-line maintenance treatment ovarian cancer exceeded our expectations in terms of significant improvement in PFS vs placebo in each of the primary efficacy populations, including the all-comers or intent-to-treat population. We believe that the positive results from ATHENA-MONO demonstrate that [rucaparib] will provide an important new treatment option for women with advanced ovarian cancer in the first-line maintenance setting, and we look forward to submitting these data to the regulatory authorities in the US and Europe during Q2 and Q3 2022, respectively,” Patrick J. Mahaffy, president and CEO at Clovis Oncology, said in a press release.
Clovis Oncology 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. News Release. Clovis Oncology. March 31, 2022. Accessed March 31, 2022. https://bit.ly/3iRZ6EB