Treatment with rucaparib led to an improvement in investigator-assessed progression-free survival compared with chemotherapy in patients with relapsed ovarian cancer with a BRCA mutation who have received 2 or more prior lines of chemotherapy, meeting the primary end point of the phase 3 ARIEL4 clinical trial.
Treatment with rucaparib (Rubraca) led to an improvement in investigator-assessed progression-free survival (PFS) compared with chemotherapy in patients with relapsed ovarian cancer with a BRCA mutation who have received 2 or more prior lines of chemotherapy, meeting the primary end point of the phase 3 ARIEL4 clinical trial (NCT02855944), Clovis Oncology announced in a press release.
ARIEL4 study (NCT02855944) is a multicenter, randomized study, in which women were enrolled and evaluated for PFS, efficacy of rucaparib as measured by overall survival (OS), and the safety and tolerability of the PARP inhibitor. For efficacy, 325 patients with a deleterious tumor BRCA mutation were assessed, 220 of whom received rucaparib.
“The ARIEL4 study verified that women with relapsed, BRCA mutation-positive advanced ovarian cancer, including those who are platinum-sensitive or -resistant, received benefit with rucaparib treatment when compared to chemotherapy,” stated Amit Oza, MD, head of the Division of Medical Oncology & Hematology, Medical Director of the Cancer Clinical Research Unit at Princess Margaret Cancer Centre, co-director of the Drug Development Program at PM Cancer Centre, Senior Scientist at the Princess Margaret Cancer Centre, and professor of Medicine at University of Toronto. “These results underscore the importance of rucaparib as a treatment option for women with BRCA-mutant advanced ovarian cancer.”
Rucaparib-treated patients had a higher investigator-assessed PFS that was statistically significant compared with chemotherapy (HR, 0.639; P =.0010). The median PFS observed in the rucaparib arm was 7.4 months versus 5.7 months in the chemotherapy arm.
In the intention-to-treat (ITT) population of 349 patients, 233 received rucaparib, and 116 received chemotherapy. Once again, rucaparib demonstrated statistical significance over chemotherapy in terms of investigator-assessed PFS (HR, 0.665; P =.0017).
Notably, 7 patients with BRCA reversion mutations were included in the study, but no investigator-assessed PFS benefit was observed in the subgroup.
In terms of the secondary end points of the trial, a trend toward OS benefit was observed in the chemotherapy arm with 51% of the ITT population having OS events. However, crossover to rucaparib occurred for 64% of the chemotherapy arm population following progression, confounding the signal of OS benefit. In addition, an analysis of the ITT population showed more OS benefit with rucaparib compared with chemotherapy at any point in the trial.
The safety analysis showed that both rucaparib as well as chemotherapy of either cisplatin, carboplatin, the combination of cisplatin and carboplatin, or the combination of cisplatin and gemcitabine had consistent toxicity profiles to what has previously been reported. In the rucaparib arm, the most common treatment-emergent adverse events observed were anemia with decreased hemoglobin (22%), neutropenia with decreased absolute neutrophil count (10%), asthenia and fatigue (8%), thrombocytopenia and decreased platelets (8%), and increased alanine aminotransferase and aspartate aminotransferase (8%).
“We are pleased with these topline results from the ARIEL4 trial, which confirm the clinical benefit of Rubraca versus chemotherapy, including platinum-based chemotherapy, as a treatment for women with BRCA mutation-positive advanced ovarian cancer, including patients who are platinum-resistant,” said Patrick J. Mahaffy, president, and chief executive officer, Clovis Oncology, in a statement. “We look forward to sharing comprehensive results at an upcoming medical meeting,” Mahaffy added.
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. News release. Clovis Oncology, Inc. December 21, 2020. Accessed December 21, 2020. https://bit.ly/3h4G4t2