Final safety results from ATHENA–MONO (GOG-3020/ENGOT-ov45), a randomized, placebo-controlled, double-blind, phase 3 trial evaluating rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer.

Abstract

5554 Background: Rucaparib provided a sustained progression-free survival benefit in patients (pts) with newly diagnosed advanced ovarian cancer after first-line treatment in the phase 3 ATHENA-MONO study (NCT03522246). We report final safety analyses (data cutoff 09 Mar 2023). Methods: Rucaparib was administered in 28-day cycles. Eligible pts were randomized 4:1 to oral rucaparib 600 mg BID (N=427) or placebo (N=111), with a treatment cap defined as 24 months. The safety population included randomized pts who received at least 1 dose of study drug (rucaparib, n=425; placebo, n=110). Results: All ATHENA-MONO pts discontinued treatment as of 24 Nov 2022 with a median treatment duration of 15 months and 35% of pts reaching the 24-month treatment cap. The median (range) relative dose intensity was 89% (30-110) for rucaparib. The rate of treatment-emergent adverse events (TEAEs), grade ≥3 TEAEs, TEAEs leading to interruption, dose reduction, or discontinuation with rucaparib remained consistent with the primary endpoint analysis with some minor changes (see Table below). Most common grade ≥3 TEAEs were anemia/decreased hemoglobin (28.7%), neutropenia/decreased neutrophils (14.6%), increased ALT/AST (10.6%), and thrombocytopenia/decreased platelets (7.3%). The most common TEAEs leading to discontinuation were anemia/decreased hemoglobin (3.5%), asthenia/fatigue (4.9%), and nausea (2.1%). Hypertension continued to be the most common TEAE observed in the placebo group (3.6%) compared with 1.6% in the rucaparib group. There were no changes in the incidence of serious adverse events or TEAEs leading to death since the primary endpoint analysis. Myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) were reported in a total of 3 pts in the rucaparib group (1 MDS during treatment [0.2%] and 1 AML and 1 MDS during long-term follow-up [0.5%]), of which the latter occurred since the primary readout. The initial MDS event that occurred during treatment, included in these incidence numbers, was considered resolved by the investigator since the initial analysis. Conclusions: Long-term maintenance treatment with rucaparib demonstrates a consistent and manageable safety profile in a broad population of pts with newly diagnosed ovarian cancer. No new safety signals were identified. Adverse events were generally manageable and led to discontinuation in a low proportion of pts. Clinical trial information: NCT03522246 . [Table: see text]