The U.S. Food and Drug Administration (FDA) granted accelerated approval to rucaparib in May 2020 for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic)-associated metastatic castrate resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and taxane. This approval was based on data from the ongoing multi-center, open-label single-arm trial, TRITON2. The primary endpoint confirmed objective response rate, in the 62 patients who met the above criteria, was 44% (95% confidence interval [CI]: 31%-57%). The median duration of response was not estimable (95% CI: 6.4-NE). Fifty-six percent of patients had a response duration of >6 months and 15% >12 months. The safety profile of rucaparib was generally consistent with that of the class of poly-(ADP-ribose) polymerase (PARP) enzyme inhibitors and other trials of rucaparib in the treatment of ovarian cancer. Deaths due to adverse event (AE) occurred in 1.7% of patients and 8% discontinued rucaparib due to an AE. Grade 3-4 AEs occurred in 59% of patients. No patients with prostate cancer developed myelodysplastic syndrome or acute myeloid leukemia. The trial TRITON3 in patients with mCRPC is ongoing and is planned to verify the clinical benefit of rucaparib in mCRPC. This article summarizes the FDA thought process and data supporting this accelerated approval. IMPLICATIONS FOR PRACTICE: The accelerated approval of rucaparib for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic)-associated mCRPC who have been treated with androgen receptor-directed therapy and a taxane represents the first approved therapy for this selected patient population. This approval was based on a single-arm trial demonstrating a confirmed objective response rate greater than that of available therapy with a favorable duration of response and an acceptable toxicity profile. The ongoing trial TRITON3 is verifying the clinical benefit of this drug.
The oncologist. 2020 Nov 04 [Epub ahead of print]
Mitchell S Anscher, Elaine Chang, Xin Gao, Yutao Gong, Chana Weinstock, Erik Bloomquist, Oluseyi Adeniyi, Rosane Charlab, Sarah Zimmerman, Maritsa Serlemitsos-Day, Yang Min Ning, Ruth Mayrosh, Barbara Fuller, Ann Marie Trentacosti, Pamela Gallagher, Karen Bijwaard, Frances Fahnbulleh, Felicia Diggs, Shaily Arora, Kirsten B Goldberg, Shenghui Tang, Laleh Amiri-Kordestani, Richard Pazdur, Amna Ibrahim, Julia A Beaver
Center for Drug Evaluation and Research., Oncology Center of Excellence.