The US Food and Drug Administration (FDA) has approved the use of rucaparib (Rubraca, Clovis Oncology) tablets for maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy, regardless of BRCA status. No biomarker testing is needed for the drug to be prescribed.
Rucaparib previously had been granted accelerated approval for the treatment of advanced ovarian cancer in patients who have received two or more prior chemotherapies and whose tumors have a BRCA gene mutation. Biomarker testing is required in this case.
“This FDA approval provides a meaningful advancement for the treatment of women with recurrent ovarian cancer, offering them the potential to reduce their risk of disease progression following platinum-based chemotherapy,” said Patrick J Mahaffy, CEO and president of Clovis Oncology, in a statement. “We are grateful that the FDA expedited review of this maintenance treatment indication, so that physicians can begin offering it to appropriate patients beginning today.”
Rucaparib is a poly-adenosine diphosphate-ribose polymerase (PARP) inhibitor that blocks an enzyme that would otherwise help repair damaged DNA in cancer cells, and thus the drug may slow or stop tumor growth.
ARIEL3 Showed Efficacy
The maintenance treatment approval is based on findings from the ARIEL3 study, which evaluated the agent as maintenance treatment in 564 patients (561 in the final analysis). In this phase 3 study, 375 (66%) patients were randomly assigned to 600 mg of rucaparib twice daily and 189 (34%) to placebo.
Progression-free survival was 10.8 months in the intention-to-treat population vs 5.4 months in the placebo group (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.30 – 0.45; P < .0001).
In the nested BRCA-mutant cohort, the median progression-free survival in patients with a BRCA-mutant carcinoma was 16.6 months for patients receiving rucaparib vs 5.4 months for the placebo group (HR, 0.23; 95% CI, 0.16 – 0.34; P < .0001).
In addition, complete responses in the rucaparib group were observed in 7 (18%) patients who had measurable disease at baseline in the nested BRCA-mutant cohort, 10 (12%) in the homologous recombination deficiency cohort, and 10 (7%) in the intention-to-treat population. This is in comparison to only 1 (2%) complete response among placebo patients in the intention-to-treat population.
Initial results from the ARIEL3 clinical trial were released by the manufacturer in June 2017. Additional trial data were presented at the 2017 European Society for Medical Oncology (ESMO) Annual Conference in Madrid, Spain, and subsequently published in The Lancet.
The safety and tolerability of rucaparib were consistent with those previously reported, and there were no new safety signals. The most common adverse reactions (grade 1 – 4) were nausea, fatigue/asthenia, abdominal pain/distention, rash, dysgeusia, anemia, elevated aspartate aminotransferase/alanine aminotransferase levels, constipation, vomiting, diarrhea, thrombocytopenia, nasopharyngitis/upper respiratory tract infection, stomatitis, decreased appetite, and neutropenia. Most of the adverse reactions and laboratory abnormalities were grade 1 or 2.
However, rucaparib has been associated with hematologic toxicity, including myelodysplastic syndrome and acute myeloid leukemia (AML). Myelodysplastic syndrome/AML was reported in 2 of 377 (0.5%) patients with ovarian cancer treated with rucaparib. In addition, AML was reported in 2 (<1%) patients, and 1 case of AML was fatal.
“The FDA approval of Rubraca in the maintenance treatment setting is an important milestone for physicians and their patients with recurrent ovarian cancer because it offers them greater flexibility to use this novel PARP inhibitor, which has demonstrated significant clinical efficacy and has been well received in practice,” said Jonathan Ledermann, MD, professor of medical oncology, clinical director, UCL Cancer Institute, London, United Kingdom, and a principal investigator for the ARIEL3 study.
“This will enable physicians to offer Rubraca to more women with platinum-sensitive, recurrent ovarian cancer,” Ledermann commented in a statement.
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