Rucaparib improves progression-free survival (PFS) compared to chemotherapy in patients with relapsed BRCA-mutated ovarian cancer, according to results from the ARIEL4 study.
“The ARIEL4 Study is great news for practices and patients across the country as it provides even more confidence in rucaparib, as the first to beat a platinum-based chemotherapy, providing an impactful treatment option for patients with BRCAmut-associated advanced ovarian cancer. Clovis Oncology continues to provide best-in-class medicines, at the earliest point possible, in order to improve patient outcomes.” said Bradley J. Monk, MD, Professor at University of Arizona and Head of the US Oncology Gynecologic Research Committee.
The ARIEL4 study is a multicenter, randomized, phase 3 study evaluating rucaparib versus chemotherapy in platinum-sensitive, partially platinum-sensitive and platinum-resistant patients with relapsed ovarian cancer and a BRCA mutation, who have received ≥2 prior lines of chemotherapy.
The primary end point of the study is investigator-assessed PFS with a step-down analysis from the efficacy population to the intention-to-treat (ITT) population. The efficacy population included patients with a deleterious tumor BRCA mutation and excluded those with a BRCA reversion mutation. Overall survival (OS) is a secondary end point.
A total of 349 patients from North and South America, Europe, and Israel were enrolled in the study (ITT population).
The efficacy population consisted of 325 patients. For the primary end point of PFS, the rucaparib group (n = 220) achieved statistical significance compared with chemotherapy (n = 105) with a hazard ratio (HR) of .639 (P = .0010). Median PFS in this population was 7.4 months versus 5.7 months, respectively.
Additionally, for the primary end point of PFS in the ITT population, the rucaparib group (n = 233) achieved statistical significance compared with chemotherapy (n = 116) with a HR of .665 (P = .0017). Median PFS in this population was 7.4 months versus 5.7 months, respectively.
An interim analysis showed a trend toward an OS advantage in the chemotherapy group but was confounded by the high rate (64%) of per-protocol crossover to rucaparib following progression on chemotherapy. An analysis of the ITT population showed a trend toward an OS advantage for those patients who received rucaparib at any point in the trial compared to those who did not.
“The ARIEL4 Study Results released today by Clovis Oncology are another important step forward for patients with ovarian cancer, especially those with a BRCA germline or somatic (tissue) mutation. These results reiterate the important option to being able to use a non-chemotherapy regimen, like the PARP inhibitor rucaparib, for treatment. ARIEL4 showed a benefit in women with relapsed, BRCA-mutant advanced ovarian cancer who are platinum-resistant or platinum sensitive.” said David O’Malley, MD, Director of the Division on Gynecologic Oncology at The Ohio State University. “Additionally, the ARIEL4 study highlighted the benefit of identifying BRCA reversion mutations which will help determine appropriate treatment decisions prospective.”
Adverse events (AEs) were consistent with known safety profiles of rucaparib and chemotherapy. The most common grade 3/4 AEs among all patients treated with rucaparib (n = 232) were anemia/decreased hemoglobin (22%), neutropenia/decreased absolute neutrophil count (10%), asthenia/fatigue (8%), thrombocytopenia/decreased platelets (8%), and increased ALT/AST (8%).
Source: Business Wire. Clovis Oncology’s Rubraca® (Rucaparib) Met The Primary Endpoint Of Significantly Improving Progression-Free Survival Vs. Chemotherapy In The ARIEL4 Randomized Phase 3 Treatment Study In Later-Line Ovarian Cancer Patients With A BRCA Mutation. December 21, 2020. https://ir.clovisoncology.com/investors-and-news/news-releases/press-release-details/2020/Clovis-Oncologys-Rubraca-rucaparib-Met-the-Primary-Endpoint-of-Significantly-Improving-Progression-Free-Survival-vs.-Chemotherapy-in-the-ARIEL4-Randomized-Phase-3-Treatment-Study-in-Later-line-Ovarian-Cancer-Patients-with-a-BRCA-mutation/default.aspx. Accessed December 29, 2020.
