Rucaparib maintains PFS benefit at 4 years in stage III/IV ovarian cancer

Treatment with rucaparib in patients with newly diagnosed advanced ovarian cancer provides long-term improvements in progression-free survival (PFS) both in those with high and low risk of disease progression, as shown in the updated PFS analyses of the ATHENA-MONO study. 

In addition, rucaparib demonstrates an acceptable safety profile, with no new safety signal observed, according to lead investigator Dr Rebecca Kristeleit from Guy’s and St Thomas’ NHS Foundation Trust, London, UK, who presented the findings at the recent ESMO Gynaecological Cancers Congress 2024. 

The initial analysis of the ATHENA-MONO study revealed a sustained PFS benefit in patients with advanced ovarian cancer following first-line treatment with rucaparib.  

In the current analysis, patients with high-grade, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage III-IV ovarian cancer, who showed response to first-line treatment, were randomly assigned in a 4:1 ratio to receive either rucaparib 600 mg BID (n=427) or placebo (n=111) for up to 2 years. 

Kristeleit and her team then performed an exploratory analysis to examine the updated investigator-assessed PFS, which included the primary populations (homologous recombination deficiency [HRD] and intent-to-treat [ITT]), non-nested HRD subgroups, as well as low- or high-risk patients according to FIGO stage or surgical outcome and surgery timing. 

Recurrence-free survival for patients with complete response at baseline was defined as time from randomization to disease recurrence (ie, new lesions by imaging) or death. 

Improved PFS 

Median PFS after a median of 4.0 and 3.5 years of follow-up (an additional 1.9 and 1.6 years of follow-up, respectively) was either longer or not reached in the rucaparib arm than in the placebo arm, both in ITT populations and in the HRD and non-nested HRD subgroups. [ESMO Gyn 2024, abstract 49M0] 

At 4 years, 27.7 percent of patients treated with rucaparib in the higher-risk subgroup achieved progression-free status as opposed to 8.6 percent of those treated with placebo, while the corresponding rates in the lower-risk subgroup were 41.9 percent and 37.2 percent. 

“Rucaparib maintained a clinically significant improvement in PFS at 4 years follow-up in patients with newly diagnosed advanced ovarian cancer in the overall population and all subgroups presented,” said Kristeleit. 

In addition, 35 percent of patients in the rucaparib arm achieved the 2-year treatment cap as compared with 17 percent in the placebo arm, while the rates of complete remission at 4 years were 29 percent and 12 percent, respectively. 

Notably, the risk of disease recurrence or death decreased by 51 percent among patients in complete response at baseline. The safety profile of rucaparib was also consistent with that from the primary endpoint analysis, according to Kristeleit. [O’Malley, et al, ASCO 2024] 

However, three new cases of myelodysplastic syndrome or acute myeloid leukaemia occurred since the primary analysis. Such incidence was the same in both rucaparib and placebo arms (<1 percent).