Trial Confirms Rubraca’s Clinical Benefit Over Chemotherapy

Trial Confirms Rubraca’s Clinical Benefit Over Chemotherapy

Rubraca (rucaparib) is superior to chemotherapy at prolonging life without disease worsening in people with advanced ovarian cancer who received at least two prior lines of chemotherapy, according to top-line data from an ongoing Phase 3 trial.

Data from the study, called ARIEL4 (NCT02855944), also showed that Rubraca’s safety profile in these women, whose tumors contained mutations in the BRCA DNA repair gene, was consistent with that reported on the therapy’s approved label in Europe and the U.S.

“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,” Patrick J. Mahaffy, president and CEO of Clovis Oncology, which developed the therapy, said in a press release.

Rubraca is an oral, small molecule inhibitor of PARP enzymes. These enzymes are involved in DNA repair and in the control of programmed cell death. By blocking the activity of PARP enzymes, Rubraca is designed to prevent cancer cells from repairing their DNA, eventually killing them.

Due to this mechanism of action, Rubraca is particularly effective at treating patients whose tumors contain mutations in DNA repair genes, such as BRCA1 and BRCA2.

Rubraca was originally approved in the U.S. and Europe as a treatment for women with advanced ovarian cancer who had previously received at least two lines of chemotherapy and whose tumors contained BRCA mutations.

Later, the medication’s approval was extended in both regions, to allow Rubraca to be given as a maintenance therapy to treat women with recurrent, platinum-sensitive ovarian cancer, regardless of BRCA mutation status.

ARIEL4 is a post-marketing confirmatory trial that aimed to demonstrate Rubraca’s superiority over chemotherapy at prolonging the time women with advanced ovarian cancer live without showing signs of disease progression. This endpoint was evaluated in a subset of patients who had deleterious BRCA mutations (mutations that rendered BRCA proteins unable to repair DNA), as well as in the overall population including patients with other forms of BRCA mutations.

The trial’s overall population comprised a total of 349 women with either platinum-sensitive or resistant ovarian cancer, whose disease had returned after receiving two or more prior lines of chemotherapy.

From these, 325 were part of the group with deleterious BRCA mutations. In this subgroup, Rubraca significantly prolonged the time lived without worsening from a median of 5.7 months (on chemotherapy) to 7.4 months.

Similar analyses performed in the overall population yielded the same results, confirming Rubraca’s superiority over chemo at delaying disease worsening or death in this patient population.

“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,” said Amit Oza, MD, from the Princess Margaret Cancer Centre, who’s also a professor of medicine at the University of Toronto, and coordinating investigator on ARIEL4.

“These results underscore the importance of rucaparib as a treatment option for women with BRCA-mutant advanced ovarian cancer,” he added.

As expected, Rubraca provided minor clinical benefits in the small group of women (around 7% of the study’s overall population) whose tumors contained BRCA reversion mutations (mutations that restore the function of BRCA proteins in cancer cells, rendering tumors more resistant to treatments).

“The ARIEL4 data confirm the clinical relevance of BRCA reversion mutations and advance our understanding of how best to manage the treatment of women with advanced ovarian cancer,” said Rebecca Kristeleit, PhD, consultant medical oncologist, and co-chief investigator of ARIEL4.

Additional analyses also revealed that women who were treated with Rubraca at some point during ARIEL4 tended to live longer than those who did not.

Reported adverse events were consistent with the known safety profile of Rubraca and chemotherapy. The most common serious and life-threatening side effects observed in the trial were anemia (22%), low white blood cell counts (10%), fatigue (8%), low platelet counts (8%), and high levels of liver enzymes (8%).

Clovis Oncology is now planning to submit detailed findings from ARIEL4 to be presented at a future medical meeting in 2021.

“We look forward to sharing comprehensive results at an upcoming medical meeting,” Mahaffy said.