Drugmaker Pulls Third-Line PARP Inhibitor Approval in Ovarian Cancer

— Decision on rucaparib follows negative OS signal and "discussions" with FDA

by Mike Bassett, Staff Writer, ľ��ֱ�� June 17, 2022

Clovis Oncology has voluntarily withdrawn the indication for rucaparib (Rubraca) as a third-line treatment in BRCA-mutated ovarian cancer after an overall survival (OS) analysis showed a signal for potential harm, according to a .

"Based on further discussions with the FDA following submission of ARIEL4 OS data previously disclosed, the Company elected to voluntarily withdraw the approval for Rubraca in the U.S. as treatment of BRCA-mutated ovarian cancer after two or more chemotherapies," Clovis wrote in its filing.

"This withdrawal became effective as of June 10, 2022 and does not affect other indications for Rubraca," Clovis noted. The PARP inhibitor also as a maintenance therapy in recurrent ovarian cancer and as a later-line treatment in metastatic prostate cancer for patients with germline or somatic BRCA mutations.

Primary results from reported last year showed that third-line rucaparib led to a median progression-free survival (PFS) of 7.4 months versus 5.7 months with chemotherapy in ovarian cancer patients with BRCA-mutant disease.

At that time, however, OS data were immature. In an earlier SEC filing, Clovis reported a 31% higher risk of death for the rucaparib group in an intent-to-treat (ITT) analysis of ARIEL4 (HR 1.31, nominal P=0.0507), which appeared largely driven by the platinum-resistant subgroup (HR 1.51, nominal P=0.0251).

The negative OS signal may potentially derail the company's bid for approval as first-line maintenance in platinum-sensitive ovarian cancer based on findings from the phase III ATHENA-MONO trial. The study showed a doubling in median PFS with the PARP inhibitor versus placebo for both the ITT population (20.2 vs 9.2 months) and for the subgroup with homologous repair-deficient (HRD) tumors (28.7 vs 11.3 months, respectively). OS was a secondary endpoint and data are immature.

According to Clovis, the FDA said the company should not submit for approval in the first-line maintenance setting until OS data from the trial are at least 50% mature or "expect the FDA to require a discussion" with its Oncologic Drugs Advisory Committee.

Currently, the OS data are approximately 25% mature and Clovis estimates that 50% maturity won't be reached for another 2 years.

Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.