Primary results of rucaparib in ovarian cancer 

First-line rucaparib maintenance therapy after platinum-based chemotherapy improved the progression-free survival (PFS) of patients with stage III–IV ovarian cancer in the ATHENA-MONO trial. Further tumour reductions were reported following treatment with rucaparib.  

The efficacy of the PARP inhibitor rucaparib has been established in patients with platinum-sensitive recurrent ovarian cancer [1]. Also, PARP inhibitors have delivered PFS benefits as first-line maintenance treatment [2]. However, the optimal first-line maintenance strategy for patients with advanced ovarian cancer is still unclear.

The phase 3 ATHENA trial (NCT03522246) randomised patients with FIGO stage III or IV ovarian cancer, who responded to first-line platinum-based doublet chemotherapy, 4:4:1:1 to rucaparib plus nivolumab (arm A), rucaparib plus placebo (arm B), placebo plus nivolumab (arm C), and placebo plus placebo (arm D). Prof. Bradley Monk (University of Arizona, AZ, USA) discussed the results of the ATHENA-MONO trial, comparing arm B (n=427) with arm D (n=111) [3]. Investigator-assessed PFS was the primary outcome of the trial.

Rucaparib was associated with an improvement in the median PFS of patients with homologous recombination deficiency-positive tumours (28.7 vs 11.3 months; HR 0.47; P=0.0004) and in the median PFS of the intention-to-treat population (20.2 vs 9.2 months; HR 0.52; P<0.0001). The PFS per blinded, independent, central review demonstrated similar results. Furthermore, the PFS benefit of rucaparib was consistent among BRCA-mutated (HR 0.40), BRCA wildtype/loss of heterozygosity high (HR 0.58), and homologous recombination deficiency-negative patients (HR 0.65). Prof. Monk pointed out that patients with the highest risk (residual disease, stage IV, abnormal CA-125 levels) appeared to benefit more from treatment with rucaparib.

In total, 60.5% of the patients on rucaparib experienced grade ≥3 adverse events (AEs) compared with 22.7% of the patients in the placebo arm. Most treatment-emergent AEs in the active arm were of gastrointestinal origin or marrow-related, and could be mitigated with dose reductions or dose interruptions. The discontinuation rate was 11.8% in patients receiving rucaparib.

Rucaparib showed to be effective as first-line maintenance monotherapy with significant benefits over placebo in the intention-to-treat and homologous recombination deficiency patients.

1. Coleman RL, et al. Lancet. 2017;390:1949‒1961. 
2. Moore K, et al. N Engl J Med. 2018;379:2495‒2505. 
3. Monk BJ, et al. ATHENA–MONO (GOG-3020/ENGOT-ov45): A randomized, double-blind, phase 3 trial evaluatingrucaparibmonotherapy versus placebo as maintenance treatment following response to first-line platinum-basedchemotherapy in ovariancancer. LBA5500, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.

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Posted on 5 August, 2022