Rubraca extends PFS as maintenance therapy in ovarian cancer, topline data show
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Rucaparib monotherapy significantly extended PFS compared with placebo as first-line maintenance treatment for women with ovarian cancer, according to topline data from the randomized phase 3 ATHENA-MONO trial.
Researchers observed the benefit in primary efficacy analyses of two molecularly defined subgroups of newly diagnosed women with advanced disease following platinum-based chemotherapy, including those with homologous recombination deficiency (HRD)-positive tumors and the overall intent-to-treat population. Exploratory subgroups of women with HRD-negative and BRCA-mutated tumors also achieved significant PFS benefit with rucaparib (Rubraca, Clovis Oncology), an oral, small molecule poly(ADP-ribose) polymerase (PARP) inhibitor.
“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, professor at Creighton University School of Medicine and University of Arizona College of Medicine, director of gynecologic oncology research at US Oncology Network and co-director of the Gynecologic Oncology Group, as well as global primary investigator of the ATHENA trial, said in a Clovis Oncology press release. “The results of ATHENA-MONO address many of these unanswered questions and [expand] the opportunity for rucaparib in all patients, regardless of biomarker status.”
The ATHENA-MONO trial included 538 women with high-grade ovarian, fallopian tube or primary peritoneal cancer randomly assigned to rucaparib (n = 427) or placebo (n = 111). In a step-down fashion, the primary efficacy analyses evaluated women with HRD-positive tumors, including BRCA mutations, and all randomly assigned women.
PFS served as the primary endpoint.
Among women with HRD-positive tumors, results showed significantly longer PFS by investigator review in the rucaparib group (n = 185) compared with the placebo group (n = 49), with an HR of 0.47 (95% CI, 0.31-0.72). Median PFS was 28.7 months vs. 11.3 months (P = .0004).
Researchers also observed a significant PFS benefit with rucaparib among all women studied (HR = 0.52; 95% CI, 0.4-0.68; median, 20.2 months vs. 9.2 months; P < .0001) and in exploratory subgroups of 238 women with HRD-negative tumors (HR = 0.65; 95% CI, 0.45-0.95; median, 12.1 months vs. 9.1 months; P = .0284) and 115 women with BRCA-mutant tumors (HR = 0.4; 95% CI, 0.21-0.75; median, not reached vs. 14. 7 months; P = .0041).
The most common grade 3 or grade 4 treatment-emergent adverse events among women treated with rucaparib monotherapy in the ATHENA study included anemia/decreased hemoglobin (28.7%), neutropenia (14.6%), alanine aminotransferase/aspartate transaminase increase (10.6%) and thrombocytopenia (7.1%). A higher proportion of patients in rucaparib group discontinued treatment because of treatment-emergent adverse events (11.8% vs. 5.5%), and 0.2% in the rucaparib group experienced treatment-emergent myelodysplastic syndrome/acute myeloid leukemia.
The data have been submitted for presentation at this year’s ASCO Annual Meeting.
“We believe that the positive results from ATHENA-MONO demonstrate that Rubraca 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 U.S. and Europe during Q2 and Q3 2022, respectively,” Patrick J. Mahaffy, president and CEO of Clovis Oncology, said in the press release.
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