The Italian Medicines Agency (AIFA) has approved Clovis Oncology’s Rubraca (rucaparib) for reimbursement in Italy as a maintenance therapy for women with relapsed ovarian cancer who responded to platinum-based chemotherapy, regardless of their BRCA status.
This follows Rubraca’s approval for that indication by the European Commission early this year.
“The reimbursement of Rubraca in Italy is an important step in the ovarian cancer treatment pathway, as it has shown to be effective across a broad population of women with relapsed ovarian cancer,” Patrick J. Mahaffy, Clovis Oncology’s president and CEO, said in a press release.
“We are working to make Rubraca available to as many eligible patients as possible across Europe, and we look forward to additional country launches in the coming months,” Mahaffy added.
Ovarian cancer is the eighth most commonly occurring cancer in women worldwide and is associated with a five-year survival rate of less than 50%. It is estimated that 5,000 women are diagnosed with ovarian cancer in Italy every year, and that their five-year survival rate is 39%, falling to 31% at 10 years.
Rubraca is a PARP inhibitor that works by blocking the activity of the PARP enzyme — a DNA damage sensor. That leads to the accumulation of DNA damage, and ultimately the death of cancer cells.
PARP inhibitors are particularly effective in cancer cells with defects in other DNA repair mechanisms — such as those with mutations in the BRCA1 and BRCA2 genes — due to their reliance on PARP to survive and proliferate. Mutations in the BRCA1 and BRCA2 genes are estimated to occur in 25% of ovarian cancer patients.
The presence of BRCA mutations has been associated with better treatment responses, likely due to a larger number of potential therapies. Conversely, most patients without BRCA mutations have a worse prognosis and limited therapeutic options.
Rubraca was approved for the treatment of women with BRCA-mutated advanced ovarian cancer by the U.S. Food and Drug Administration (FDA) in 2016 and by the European Commission in 2018. More recently, Rubraca’s indication was extended in the U.S. and in the European Union to include its use as maintenance treatment for women with recurrent, platinum-sensitive, ovarian cancer, regardless of BRCA status.
These approvals cover patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer.
This second indication was based on positive data from the ARIEL3 Phase 3 trial (NCT01968213). That trial evaluated the effects of Rubraca maintenance therapy, compared with a placebo, in 564 women with recurrent ovarian cancer who responded to previous platinum-based chemotherapy. A total 375 women were given Rubraca and 189 received a placebo, both delivered as 600 mg tablets twice daily.
The results showed that Rubraca treatment significantly extended the time women lived without signs of disease progression from 5.4 months to 10.8 months. That represented a 64% reduction in the risk of disease progression or death. Data from an independent radiological review indicated that Rubraca treatment extended patients’ disease-free survival even further, reaching a median of 13.7 months.
Importantly, this survival benefit was seen in the overall population, regardless of BRCA status. Nevertheless, Rubraca treatment led to better responses in women with BRCA mutations, delaying disease progression from 5.4 months to 16.6 months.
Rubraca’s overall safety profile was based on data from 937 ovarian cancer patients treated with Rubraca in clinical trials. The therapy was generally well-tolerated, with most adverse events being mildly to moderately severe. Fatigue and physical weakness, vomiting, anemia, and abdominal pain were the most common adverse events.
“In the ARIEL3 study, in fact, rucaparib doubled disease-free time after a second line of chemotherapy compared to placebo and with a manageable tolerability profile despite a study population very similar to clinical practice, regardless of the BRCA mutation,” said Nicoletta Colombo, director of the oncological gynecology program of the European Institute of Oncology in Milan.
“The fact that rucaparib is a reimbursable drug makes it an important new treatment option, even for these patients [without BRCA mutations] who still too often do not receive safe and effective maintenance therapy,” said Sandro Pignata, director of medical oncology of the urogynecology department at the National Oncological Institute Pascale Foundation in Naples, Italy.