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FDA Actions & Updates

The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Sunday, January 27, 2019

European Commission Authorizes Rucaparib Tablets as Maintenance Treatment for Relapsed Ovarian Cancer

The European Commission (EC) has approved the use of rucaparib for a second indication, as monotherapy for the maintenance treatment of adults with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

This expands rucaparib's indication beyond its initial marketing authorization in Europe granted in May 2018 and with this label expansion, rucaparib is now available to patients regardless of their BRCA mutation status.

The EC authorization is based on data from the phase III ARIEL3 clinical trial, which found that rucaparib significantly improved progression-free survival in all ovarian cancer patient populations studied.

The ARIEL3 trial was a double-blind, placebo-controlled clinical trial of rucaparib that enrolled 564 women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in complete or partial response to platinum-based chemotherapy. Patients were randomized (2:1) to receive rucaparib tablets 600mg twice daily (n=375) or placebo (n=189).

ARIEL3 successfully achieved its primary endpoint, of extending investigator-assessed progression-free survival (PFS) versus placebo in all patients treated (intention-to-treat [ITT]), population, regardless of BRCA status; the key secondary endpoint of extending PFS as assessed by independent radiological review (IRR) was also achieved.

An exploratory analysis of patients in the ITT population with measurable disease at baseline showed a tumor response was reported in 18 percent (95% CI 12%–26%) of patients (n=26) on rucaparib compared to 8 percent (95% CI 3% – 17%) of patients (n=5) on placebo (p value = 0.0069), including 10 patients (7%) in the rucaparib group who achieved a complete remission.

The overall safety profile of rucaparib is based on data from 937 patients with ovarian cancer treated with rucaparib monotherapy in clinical trials. Adverse reactions occurring in ≥20 percent of patients were nausea, fatigue/asthenia, vomiting, anemia, abdominal pain, dysgeusia, alanine aminotransferase (ALT) elevations, aspartate aminotransferase (AST) elevations, decreased appetite, diarrhea, thrombocytopenia, and creatinine elevations. The majority of adverse reactions were mild to moderate (Grade 1 or 2).

Grade ≥3 adverse reactions occurring in >5 percent of patients were anemia (23%), ALT elevations (10%), fatigue/asthenia (10%), neutropenia (8%), thrombocytopenia (6%), and nausea (5%). The only serious adverse reaction occurring in > 2 percent of patients was anemia (5%).

Adverse reactions that most commonly led to dose reduction or interruption were anemia (20%), fatigue/asthenia (18%), nausea (16%), thrombocytopenia (15%), and AST/ALT elevations (10%). Adverse reactions leading to permanent discontinuation occurred in 10 percent of patients, with thrombocytopenia, nausea, anemia, and fatigue/asthenia being the most frequent adverse reactions leading to permanent discontinuation.