EMA has started a review of the cancer medicine rucaparib camsylate (Rubraca) when it is used to treat high-grade epithelial ovarian, Fallopian tubes or primary peritoneal cancer with a BRCA mutation in patients whose cancer relapsed after platinum-based chemotherapy and who can no longer tolerate these medicines.
The review follows interim results indicating that overall survival (OS) was shorter in these patients than in those receiving chemotherapy. These results come from the ongoing ARIEL4 study comparing Rubraca with chemotherapy in patients with high-grade epithelial ovarian, Fallopian tubes or primary peritoneal cancer with a BRCA mutation and relapse after chemotherapy.
While the review is ongoing, physicians are recommended not to start treatment with Rubraca in patients with platinum-sensitive, relapsed or progressive, BRCA-mutated, high-grade epithelial ovarian, Fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.
EMA will now assess all available information on the use of Rubraca as third-line treatment and recommend whether Rubraca’s marketing authorisation in the EU should be maintained or varied.
The ongoing phase III ARIEL4 study compared Rubraca with chemotherapy in patients with relapsed, BRCA-mutated, high-grade epithelial ovarian, Fallopian tube, or primary peritoneal cancer. An interim analysis of ARIEL4 found that OS for Rubraca was lower than that seen in the chemotherapy control arm, 19.6 months versus 27.1 months (hazard ratio [HR] 1.550; 95% confidence interval [CI] 1.085, 2.214). Patients included in the study were stratified at the time of randomisation according to platinum sensitivity (platinum sensitive versus partially platinum sensitive versus platinum resistant). The HRs for OS in these subgroups were 1.12 (95% CI 0.44- 2.88), 1.15 (95% CI 0.62-2.11) and 1.72 (95% CI 1.13-2.64), respectively.
In the efficacy population of the ARIEL4 study, a difference in favour of Rubraca was observed for the primary endpoint of progression-free survival (PFS) by investigator, with a reported median PFS by investigator of 7.4 months for the Rubraca group compared with 5.7 months for the chemotherapy group (HR 0.639; p = 0.0010).
There are no new safety concerns with the medicine.
This recommendation does not affect the use of Rubraca as maintenance treatment following chemotherapy.
Rubraca was granted a ‘conditional approval’ on 24 May 2018. At the time of its approval, data on the size of the effect of Rubraca were limited. The medicine was therefore granted a marketing authorisation on condition that the company provided additional data from the ARIEL4 study to confirm the safety and effectiveness of the medicine. More information about the medicine can be found here.
The review of Rubraca was initiated at the request of the European Commission, under Article 20 of Regulation (EC) No 726/2004. The review is being carried out by the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use. While the review is ongoing, the CHMP issued temporary recommendations to restrict the use of Rubraca in certain new patients as an interim measure to protect public health. The recommendation was forwarded to the European Commission (EC), which issued a temporary legally binding decision applicable in all EU Members States on 4 May 2022.
Once the CHMP review is concluded, the final opinion will then be forwarded to the EC, which will issue a final legally binding decision applicable in all EU Member States.