The European Medicines Agency Committee for Medicinal Products for Human Use has recommended that rucaparib no longer be used as monotherapy for the third-line treatment of patients with platinum-sensitive, relapsed or progressive BRCA-mutated high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer.
The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) has recommended that rucaparib (Rubraca) no longer be used as monotherapy for the third-line treatment of patients with platinum-sensitive, relapsed or progressive BRCA-mutated high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer following at least 2 lines of platinum-based chemotherapy and who cannot tolerate additional platinum-based therapy.1
The recommendation was made following the final analysis of the phase 3 ARIEL4 study (NCT02855944), in which rucaparib failed to elicit an improvement in median overall survival at 19.4 months, compared with 25.4 months for chemotherapy (HR, 1.31; 95% CI, 1.00-1.73; P = .0017).
The analysis follows a prior announcement that the study met its primary end point of progression-free survival (PFS), showing a median of 7.4 months with rucaparib vs 5.7 months with chemotherapy (HR, 0.639; P = .0010).2
Notably, the recommendation does not affect the use of rucaparib as maintenance treatment for adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.
Rucaparib received a conditional approval on May 24, 2018, with the understanding that the company provided additional data from the ARIEL4 study to confirm the safety and effectiveness of the medicine in the third-line treatment indication.
The review of rucaparib began at the request of the European Commission, under Article 20 of Regulation (EC) No 726/2004.
While the review was ongoing, the CHMP issued temporary recommendations to restrict the use of rucaparib as third-line treatment in new patients as an interim measure to protect public health. The recommendation was sent to the European Commission, which issued a temporary legally binding decision applicable in all EU Member States on May 4, 2022.
Now that the CHMP has completed its evaluation of the final study data from ARIEL4 and has issued its final recommendation, the opinion will be forwarded to the European Commission, which will announce a legally binding decision for all EU Member States.
The multicenter, phase 3 trial evaluated 600 mg of oral rucaparib twice daily vs physician’s choice of chemotherapy in patients with platinum-sensitive, partially platinum-sensitive, and platinum-resistant, relapsed ovarian cancer harboring a BRCA mutation who had previously received 2 or more lines of chemotherapy. Physician’s choice of chemotherapy consisted of cisplatin; carboplatin; carboplatin/paclitaxel; carboplatin/gemcitabine; cisplatin/gemcitabine; or paclitaxel.3
Eligible patients had to be aged 18 years, have a histologically confirmed diagnosis of high-grade serous or grade 2 or 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer, have received 2 prior chemotherapy regimens, and have either relapsed or progressed on treatment.
The primary end point of the trial was investigator-assessed PFS, with a step-down analysis from the efficacy population, if significant, to the intention-to-treat (ITT) population.
A total of 349 patients were enrolled to the trial, and 325 were included in the efficacy population, the latter of which comprised the group of patients with a deleterious tumor BRCA mutation and excluded those with a BRCA reversion mutation.
Additional results demonstrated that in the ITT population, the median PFS was 7.4 months with rucaparib vs 5.7 months with chemotherapy (HR, 0.665; 95% CI, 0.516-0.858; P = .0017).
Regarding safety, the most common grade 3/4 treatment-emergent adverse effects in all patients who received rucaparib included anemia/decreased hemoglobin (22%), neutropenia/decreased absolute neutrophil count (10%), asthenia/fatigue (8%), thrombocytopenia/decreased platelets (8%), and increased alanine aminotransferase/aspartate aminotransferase (8%).