Rubraca (rucaparib) maintenance treatment significantly improved survival without further disease progression among ovarian cancer patients taking part in a Phase 3 clinical trial, researchers showed in a presentation at the ongoing European Society for Medical Oncology (ESMO) 2017 Congress in Madrid.
The treatment benefitted patients with different types of genetic flaws that impact their ability to repair damaged DNA.
Clovis Oncology — Rubraca’s developer — now aims to use the data to expand the drug’s regulatory approval to also include second line or later maintenance treatment, in addition to its approved use as a single therapy for ovarian cancer patients with mutations in their BRCA genes, who have received earlier chemotherapy treatment.
“These results reinforce rucaparib’s potential to provide an enduring and significant clinical benefit in women with advanced ovarian cancer, regardless of their tumor genetics,” Jonathan A. Ledermann, MD, principal investigator for the ARIEL3 study in Europe and other countries outside the U.S., who presented the data, said in a press release.
Ledermann, who is also a professor of medical oncology, and director of Cancer Research UK and UCL Cancer Trials Centre at the University College London Cancer Institute, also spoke of the drug’s ability to enhance the response to earlier chemotherapy.
“It is also clinically significant that rucaparib not only sustained patients’ most recent response to platinum, but in some trial participants also enhanced that response, including the radiological elimination of residual tumor,” he said.
The Phase 3 ARIEL3 trial (NCT01968213) included people who had responded to treatment with platinum chemotherapy.
Patients were recruited into two groups. One had BRCA mutations — known to be associated with ovarian cancer.
The other had insufficient DNA repair with high loss of heterozygosity — a term that implies that one of two gene copies are lost. This group included people with and without BRCA mutations. Researchers compared Rubraca to a placebo, and analyses also included the entire group of 564 patients in the study.
Clovis first shared data from the trial in June. The ESMO presentation included additional data from the trial.
“The comprehensive ARIEL3 results presented for the first time today demonstrate the potential of rucaparib to extend the time during which the disease is controlled for women with platinum-sensitive, advanced ovarian cancer,” Patrick J. Mahaffy, president and CEO of Clovis Oncology, said in the release.
“Very importantly, this benefit was demonstrated across all three ARIEL3 populations by both investigator review and blinded independent central assessment, including among women whose cancer does not exhibit a BRCA mutation or homologous recombination deficiency,” he added.
Among the 196 women with BRCA mutations, median progression-free survival was 26.8 months in those receiving Rubraca, as judged by a blinded independent review. In contrast, placebo-treated patients in this group survived without their cancer progressing for only 5.4 months.
Results were similar in patients with inherited and tumor-acquired BRCA mutations.
Among patients with DNA repair deficits and loss of gene copies, Rubraca was linked to a median progression-free survival of 22.9 months, compared to 5.5 months among placebo-treated patients.
Patients without BRCA mutations and a low loss of heterozygosity benefitted the least from the treatment, with a difference in improved progression-free survival rising from 5.3 months with placebo to 8.2 months with Rubraca.
Results were also significant when researchers analyzed all included Rubraca-treated patients as a single group.
“ARIEL3 shows 13.7 months — well over a year — of median PFS [progression-free survival] in the all-comers population in the trial as determined by blinded independent review, which we believe could be extremely important for women battling this difficult disease,” said Mahaffy. “We are grateful to the patients, caregivers, and investigators who participated in this study, and are working closely with European regulatory authorities to make rucaparib available to women living with ovarian cancer.”
Clovis plans to submit a supplemental New Drug Application application — covering the use of Rubraca as a second line or later maintenance treatment in ovarian cancer — with the U.S. Food and Drug Administration in October 2017. It will then seek expanded approval in Europe in early 2018.
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