KEY TAKEAWAYS
- The ARIEL3 phase 2 randomized trial with a placebo control evaluated the efficacy of rucaparib as a maintenance treatment for patients diagnosed with recurrent high-grade ovarian carcinoma.
- The study was designed for patients who responded positively to their most recent line of platinum therapy and were randomized in a ratio of 2:1 to receive either rucaparib or a placebo.
- The administration of rucaparib significantly enhanced progression-free survival and exceptional benefit in patients who exhibited favorable clinical characteristics or molecular features associated with HRD
- Rucaparib may offer substantial benefits for diverse groups with relapsed high-grade ovarian cancer, according to the researchers’ findings.
The ARIEL3 (NCT01968213) randomized trial utilized placebo control to evaluate the efficacy of the poly(ADP-ribose) polymerase inhibitor rucaparib as a maintenance treatment for patients diagnosed with recurrent high-grade ovarian carcinoma. The study is specifically designed for patients who have responded positively to their most recent line of platinum therapy. The administration of Rucaparib resulted in a notable enhancement of progression-free survival in all previously defined subgroups. Researchers examined the clinical and molecular features linked to the extraordinary efficacy of rucaparib. The subjects were subjected to randomization in a ratio of 2:1, wherein they were administered either rucaparib 600 mg twice a day or a placebo. The study also assessed the correlation between molecular features such as genomic alterations and BRCA1 promoter methylation and baseline clinical characteristics, with exceptional benefit (defined as progression-free survival of at least 2 years) versus progression on the first scan (short-term subgroup) and other efficacy outcomes.
The administration of Rucaparib demonstrated a statistically significant association with exceptional benefit compared to the placebo. Specifically, 21.1% (79 out of 375) of patients who received Rucaparib experienced exceptional benefit, while only 2.1% (4 out of 189) of patients who received the placebo experienced the same benefit (P < 0.0001). A higher occurrence of exceptional benefit was observed in patients who exhibited favorable clinical characteristics at the onset and those with carcinomas that displayed molecular indications of homologous recombination deficiency (HRD). The analysis conducted on patients who experienced exceptional benefit from rucaparib compared to those in the short-term subgroup revealed significant associations with both clinical markers (such as no measurable disease at baseline, complete response to latest platinum, and longer penultimate platinum-free interval) and molecular markers (including alterations in BRCA1, BRCA2, RAD51C, and RAD51D, as well as genome-wide loss of heterozygosity). The ARIEL3 study demonstrated a higher incidence of exceptional benefit in patients exhibiting favorable clinical characteristics or molecular features associated with homologous recombination deficiency (HRD). However, this benefit was not limited to this patient population exclusively. Researchers’ findings show that rucaparib may provide significant advantages for a broad range of individuals experiencing relapsed high-grade ovarian cancer.
Source: https://pubmed.ncbi.nlm.nih.gov/36273926/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT01968213
O’Malley DM, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, Swisher EM, Maloney L, Goble S, Lin KK, Kwan T, Ledermann JA, Coleman RL. Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian carcinoma. Gynecol Oncol. 2022 Dec;167(3):404-413. doi: 10.1016/j.ygyno.2022.08.021. Epub 2022 Oct 20. PMID: 36273926.
