Researchers found that rucaparib for patients with advanced, relapsed ovarian cancer (OC) with deleterious BRCA mutation yields significantly longer progression-free survival (PFS) than chemotherapy, according to results from the ARIEL4 study presented by Rebecca Kristeleit, PhD, UCL Cancer Institute, London, at the 2021 SGO Annual Meeting on Women's Cancer.

"ARIEL4 is a confirmatory phase III study evaluating the efficacy of rucaparib compared to standard-of-care chemotherapy in patients with BRCA-mutated relapsed ovarian cancer," explained Dr Kristeleit.

Patients were randomized 2:1 to either oral rucaparib (600mg twice daily) or standard-of-care chemotherapy. Those receiving chemotherapy with platinum-resistant or partially platinum-sensitive disease also received weekly paclitaxel 60-80 mg/2, those with fully platinum-sensitive disease received investigator's choice of platinum-based CT (single-agent carboplatin or cisplatin, or platinum doublet [carboplatin + paclitaxel, carboplatin + gemcitabine, or cisplatin + gemcitabine]). 

Prior to the study, plasma samples were assessed for BRCA reversion mutations. The primary endpoint was investigator-assessed PFS, while secondary endpoints included objective response rate (ORR) per RECIST, as well as safety. Efficacy endpoints were first evaluated in the efficacy population (randomized patients with deleterious BRCA mutations, excluding those with BRCA reversion), followed by the intent-to-treat (ITT) population.

Among the efficacy population (n=325), the investigator-assessed median PFS in the rucaparib arm (n=220) was 7.4 months (95% CI, 7.3-9.1), compared to 5.7 months (95% CI, 5.5-7.3) in the chemotherapy arm (n=105; HR, 0.64; P=0.001). The median PFS among the ITT population (n=349) was the same as the efficacy population for both the rucaparib (n=233) and chemotherapy group (n=116). 

Treatment-related adverse events were consistent with the known safety profiles of rucaparib and chemotherapy. 

“In conclusion, patients with BRCA-mutation relapsed, advanced ovarian cancer who recieved rucaparib had a significant improvement in progression-free survival versus standard-of-care chemotherapy. Overall survival from this study will be presented once death events are mature, and this is expected when at least 70% of death events have been reported,” said Dr Kristeleit.—Alexandra Graziano