Compared with placebo, maintenance rucaparib after first-line chemotherapy may improve clinical outcomes among patients with ovarian cancer, according to research presented at the 2022 ASCO Annual Meeting.
Previous research has shown that PARP inhibitors are an effective maintenance therapy after first-line treatment among patients with ovarian cancer. It was, however, formerly unclear whether all patients equally benefit from this strategy, such as those with evidence of BRCA mutations, high-risk clinical characteristics including residual disease, or homologous recombination deficiency (HRD).
The phase 3 ATHENA trial (ClinicalTrials.gov Identifier: NCT03522246) investigated the efficacy and safety of rucaparib as a maintenance therapy after first-line treatment in a broad population of patients with ovarian cancer. At ASCO 2022, Bradley J. Monk, MD, of the University of Arizona College of Medicine in Phoenix, presented the results of the ATHENA-MONO branch of the overall study.
All included patients had stage III-IV, high-grade ovarian cancer, and had completed cytoreductive surgery and at least 4 cycles of first-line platinum-doublet chemotherapy. Patients were randomly assigned 4:1 to receive maintenance oral rucaparib or placebo, and were stratified by HRD status, timing of surgery, and presence or absence of residual disease. The primary endpoint was investigator-assessed progression-free survival (PFS).
Overall, 427 and 111 patients were randomly assigned to receive rucaparib or placebo, respectively. Of these, 425 and 110 underwent treatment, and 185 and 49 people constituted the HRD population. The median times on treatment were 14.7 months in the rucaparib group compared with 9.9 months in the placebo group.
Investigator analysis showed that PFS was improved in the intent-to-treat population with rucaparib (median, 20.2 months vs 9.2 months with placebo; hazard ratio, 0.52; P <.0001), as well as in the HRD population (median, 28.7 months vs 11.3 months with placebo; P =.0004).
Blinded independent central review-assessed PFS, a secondary endpoint, appeared to support these findings, with hazard ratios for the intent-to-treat and HDR groups of 0.47 (P <.0001) and 0.44 (P =.0004), respectively, suggesting clinical benefits from rucaparib.
The most common grade 3 or worse treatment-related adverse events in the rucaparib vs placebo groups were anemia (28.7% vs 0%, respectively) and neutropenia (14.6% vs 0.9%). Both dose reduction (49.4%) and interruption (60.7%) were common in the rucaparib group.
“Rucaparib improves progression-free survival — regardless of the molecular signature,” Dr Monk concluded.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Monk BJ, Parkinson C, Lim MC, et al. ATHENA–MONO (GOG-3020/ENGOT-ov45): A randomized, double-blind, phase 3 trial evaluating rucaparib monotherapy versus placebo as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer. Presented at ASCO 2022; June 3-7, 2022. Abstract LBA5500.