Rucaparib (Rubraca▼): withdrawal of third-line treatment indication
The third-line treatment indication for rucaparib has been withdrawn following a review of the findings of the ARIEL-4 trial, which showed lower overall survival for rucaparib treatment versus standard chemotherapy in patients with high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer.
Advice for healthcare professionals:
- final analysis of the ARIEL-4 study findings showed lower overall survival with rucaparib versus standard chemotherapy control in the treatment of relapsed, BRCA-mutated, high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer
- rucaparib should no longer be used for third-line cancer treatment in new patients
- inform patients already receiving rucaparib for the third-line treatment indication of the latest data and recommendations (see letter for healthcare professionals), and consider other treatment options
- this advice does not affect use of rucaparib in maintenance of patients who are in response (complete or partial) to platinum-based chemotherapy
- continue to report any suspected adverse reactions to black triangle medicines such as Rubraca to the Yellow Card scheme
Conclusion of review of benefits and risks
Rucaparib is a Poly(ADP-Ribose) Polymerase (PARP) inhibitor used for high-grade cancers of the ovary, fallopian tubes, and the peritoneum. It targets cancer cells with mutations in the BReast CAncer (BRCA) genes. Rucaparib was granted a conditional approval in 2018, pending the ARIEL-4 study confirming its safety and effectiveness in the third-line treatment indication.
The ARIEL-4 study compared outcomes for rucaparib versus chemotherapy in treatment of patients whose cancer had relapsed after at least 2 previous treatments and who were still eligible for further chemotherapy. The final analysis showed lower overall survival with rucaparib versus chemotherapy (19.4 months versus 25.4 months, respectively, hazard ratio of 1.31 (95% CI 1.00 to 1.73; p=0.0507)).
A European review of these findings has recommended withdrawal of the third-line treatment indication since the benefits of Rubraca when used in this indication had not been confirmed and treatment may be associated with an increased risk of death. The MHRA has reviewed the recommendation and agreed with this removal of indication in the UK. See letter to UK healthcare professionals.
We understand that use of this medicine in the UK is very low. Patients who are concerned should discuss with their cancer care team or cancer specialist.
Report suspected adverse drug reactions on a Yellow Card
Rucaparib (Rubraca▼) is a black triangle medicine and all suspected adverse drug reactions should be reported to the Yellow Card scheme.
Report electronically using:
- the Yellow Card website
- the Yellow Card app; download from the Apple App Store or Google Play Store
- some clinical IT systems for healthcare professionals (EMIS, SystmOne, Vision, MiDatabank, and Ulysses)
When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.
Report suspected side effects to medicines, vaccines, medical devices and test kit incidents used in coronavirus (COVID-19) testing and treatment using the dedicated Coronavirus Yellow Card reporting site or the Yellow Card app. See the MHRA website for the latest information on medicines and vaccines for COVID-19.
Article citation: Drug Safety Update volume 16, issue 2: September 2022: 2.