The phase 3 ARIEL4 trial evaluated Rubraca (rucaparib) versus chemotherapy in patients with ovarian cancer and a BRCA mutation who did not respond to two or more lines of chemotherapy.
Rubraca (Rucaparib) improved progression-free survival compared with chemotherapy in patients whose ovarian cancer tumors harbor BRCA mutations and who had had two or more prior lines of chemotherapy, researchers say. The findings are from the ARIEL4 study, which was recently completed but is not yet published.
Women who test positive for BRCA mutations are at higher risk of developing breast or ovarian cancer compared with those who do not have this genetic mutation.
“The ARIEL4 study (results) verified that women with relapsed, BRCA mutation-positive advanced ovarian cancer, including those who are platinum-sensitive or (platinum)-resistant, received benefit with (Rubraca) treatment when compared to chemotherapy,” Dr. Amit M. Oza, head of the Division of Medical Oncology and Hematology at University of Toronto in Canada and coordinating researcher on the ARIEL4 study, said in a news release. “These results underscore the importance of (Rubraca) as a treatment option for women with BRCA-mutant advanced ovarian cancer.”
The phase 3 study evaluated 600 milligrams of Rubraca twice per day versus chemotherapy in patients with a BRCA mutation and platinum-sensitive, partially platinum-sensitive or platinum-resistant relapsed ovarian, fallopian tube or primary peritoneal cancers who have received two or more prior lines of chemotherapy. Patients who are platinum sensitive are those who responded to a platinum-based chemotherapy and had the cancer recur in six or more months, whereas those who are platinum resistant had recurrent disease within six months. Overall, 349 women were enrolled in the trial across North America, South America, Europe and Israel.
The primary end point of the study was progression-free survival, or the time since treatment when the disease does not worsen. Other outcome measures include overall survival (time a patient is alive after receiving a diagnosis or the start of treatment), objective response rate (the number of patients whose tumor size was reduced for a particular period of time), duration of response (the time when a tumor responds to treatment), patient-reported outcomes, and safety and tolerability of Rubraca versus chemotherapy.
For one analysis of progression-free survival, therapy with Rubraca (220 patients) was significantly better than chemotherapy (105 patients). The median progression-free survival was 7.4 months with Rubraca compared with 5.7 months for chemotherapy alone.
Additionally, in another analysis with 349 patients, the researcher-assessed progression-free survival in the Rubraca group (233 patients) was statistically better than the chemotherapy group (116 patients). The medians were 7.4 months versus 5.7 months, respectively.
Minimal benefit with Rubraca was noted in the 7% of patients who had a BRCA reversion mutation, or when a mutation reverts back to its original state.
Results also revealed a trend toward an overall survival advantage in the chemotherapy arm; however, this was driven by the high rate (64%) of crossover to Rubraca following disease progression with chemotherapy. When comparing patients who received Rubraca at any point on the trial with those who did not, Rubraca showed a trend toward an overall survival advantage; although numerically different, it was not statistically significant.
Regarding safety, side effects were found to be consistent with the known safety profiles of Rubraca and chemotherapy. The most common serious side effects occurring in more than 5% of all patients who received Rubraca in the ARIEL4 study were anemia (low red blood cell count; 22%), neutropenia (low count of white blood cells called neutrophils; 10%), fatigue (8%), thrombocytopenia (decreased platelets; 8%) and increased alanine transaminase/aspartate transaminase (liver enzymes that may indicate injury to the liver by the drug; 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,” Patrick J. Mahaffy, president and CEO of Clovis Oncology, said in the news release. “We look forward to sharing comprehensive results at an upcoming medical meeting.”
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