Study: Rucaparib Improves Progression-Free Survival as First-Line Maintenance Therapy in Advanced Ovarian Cancer

New research from a subgroup analysis of the phase 3 ATHENA trial has found that rucaparib (Rubraca, Clovis Oncology) as a first-line maintenance treatment improved progression-free survival (PFS) rates in women with advanced ovarian cancer across disease risk subgroups, according to data presented at the European Society of Medical Oncology (ESMO) Congress 2022.

Rucaparib is an oral, small molecular inhibitor of PARP1, PARP2, and PARP3. It is being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anticancer agents, according to a Clovis press release.

The new results in ovarian cancer reinforce the potential of rucaparib as a first-line maintenance treatment option in a broad population of patients with ovarian cancer, regardless of molecular characteristics and with or without high risk factors for progression. The trial compared rucaparib treatment versus placebo across disease risk subgroups, including surgical outcome, response to first-line chemotherapy, and additional analyses in other groups.

“These additional results from the ATHENA-MONO analysis of the phase 3 ATHENA trial demonstrate that rucaparib should be considered a new first-line maintenance treatment option for women with advanced ovarian cancer,” said ATHENA trial investigator Rebecca S. Kristeleit, MD, PhD, in a press release. “In this analysis, rucaparib prolonged [PFS] for patients with or without high risk factors for progression, irrespective of molecular characteristics, adding to our understanding of the efficacy of rucaparib in the broadest population of patients assessed in a clinical trial for first-line PARP inhibitor monotherapy.”

ATHENA is a double-blind, placebo-controlled trial of rucaparib in first-line ovarian cancer maintenance treatment. It has 2 statistically independent parts: ATHENA-MONO, which is investigating rucaparib versus placebo, and ATHENA-COMBO, which is investigating rucaparib plus nivolumab versus rucaparib alone. The new results presented at ESMO are from ATHENA-MONO.

The ATHENA-MONO trial enrolled 538 women with high-grade ovarian, fallopian tube, or primary peritoneal cancer. The primary efficacy analysis evaluated 2 prospectively defined molecular subgroups: homologous recombination deficiency (HRD)-positive, and all patients randomized in ATHENA-MONO.

PFS by Surgical Outcome

Patients who received rucaparib as maintenance therapy showed benefit regardless of surgical outcome, whether there was complete resection during cytoreductive surgery or not. Among HRD-positive patients, those who had a complete resection following cytoreductive surgery and received rucaparib have not yet reached median PFS, whereas the median PFS for patients in this group receiving placebo was 22.1 months. Among patients who did not have a complete resection following cytoreductive surgery, those in the rucaparib arm achieved a median PFS of 20.3 months, and those in the placebo arm achieved a median PFS of 9.1 months.

Among the intent-to-treat (ITT) population, patients who had a complete resection following cytoreductive surgery and who received rucaparib achieved a median PFS of 25.1 months, whereas those receiving placebo had a median PFS of 12 months. Patients in the ITT population who did not have a complete resection achieved a PFS of 13.9 months with rucaparib versus 6.4 months with placebo.

PFS by First-Line Chemotherapy Response

Researchers also analyzed PFS by first-line chemotherapy response. According to the study, patients treated with rucaparib as maintenance therapy showed benefit among all subgroups when evaluated against response per RECIST v1.1 at any time during first-line chemotherapy.

Among HRD-positive patients, those who demonstrated a partial response to first-line chemotherapy and who received rucaparib had a median PFS of 14.8 months versus 9.1 months in the placebo arm. Patients who demonstrated a complete response to first-line chemotherapy achieved a median PFS of 25.8 months with rucaparib, whereas the median PFS was not reached for patients in the placebo arm.

Among the ITT population, patients who demonstrated a partial response to first-line chemotherapy demonstrated a median PFS of 12.2 months with rucaparib versus 6.4 months with placebo. ITT patients who demonstrated a complete response to first-line chemotherapy had a median PFS of 15.6 months with rucaparib versus 6.4 months with placebo.

In addition to analyses by surgical outcome and first-line chemotherapy response, investigators conducted additional analyses in other subgroups based on baseline clinical characteristics, including International Federation of Gynecology and Obstetrics (FIGO) stage, timing of surgery, and CA-125 levels. These analyses also demonstrated that patients treated with rucaparib experienced a PFS benefit compared to patients treated with placebo. Safety was similar between subgroups.

“As further demonstrated by the additional data presented at ESMO, the ATHENA-MONO analysis continues to reinforce the potential of Rubraca as a first-line maintenance therapy for women with advanced ovarian cancer,” said Patrick J. Mahaffy, president and CEO of Clovis Oncology, in the press release. “We remain grateful to the patients who participated in the trial and for the support of the clinical community familiar with these results.”

REFERENCE

Clovis Oncology’s Rubraca (Rucaparib) As First-Line Maintenance Treatment Improves Progression-Free Survival in Women With Advanced Ovarian Cancer Across Disease Risk Subgroups. News release. Clovis Oncology; September 11, 2022. Accessed September 12, 2022. https://ir.clovisoncology.com/investors-and-news/news-releases/press-release-details/2022/Clovis-Oncologys-Rubraca-Rucaparib-as-First-Line-Maintenance-Treatment-Improves-Progression-Free-Survival-in-Women-with-Advanced-Ovarian-Cancer-Across-Disease-Risk-Subgroups/default.aspx