TY - JOUR
T1 - FDA Approval Summary
T2 - Rucaparib for the Treatment of Patients with Deleterious BRCA-Mutated Metastatic Castrate-Resistant Prostate Cancer
AU - Anscher, Mitchell S.
AU - Chang, Elaine
AU - Gao, Xin
AU - Gong, Yutao
AU - Weinstock, Chana
AU - Bloomquist, Erik
AU - Adeniyi, Oluseyi
AU - Charlab, Rosane
AU - Zimmerman, Sarah
AU - Serlemitsos-Day, Maritsa
AU - Ning, Yang Min
AU - Mayrosh, Ruth
AU - Fuller, Barbara
AU - Trentacosti, Ann Marie
AU - Gallagher, Pamela
AU - Bijwaard, Karen
AU - Philip, Reena
AU - Ghosh, Soma
AU - Fahnbulleh, Frances
AU - Diggs, Felicia
AU - Arora, Shaily
AU - Goldberg, Kirsten B.
AU - Tang, Shenghui
AU - Amiri-Kordestani, Laleh
AU - Pazdur, Richard
AU - Ibrahim, Amna
AU - Beaver, Julia A.
N1 - Publisher Copyright:
Published 2020. This article is a U.S. Government work and is in the public domain in the USA
PY - 2021/2
Y1 - 2021/2
N2 - 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 a taxane. This approval was based on data from the ongoing multicenter, 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 to not estimable). 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 enzyme inhibitors and other trials of rucaparib in the treatment of ovarian cancer. Deaths due to adverse events (AEs) occurred in 1.7% of patients, and 8% discontinued rucaparib because of 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 metastatic castrate-resistant prostate cancer 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.
AB - 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 a taxane. This approval was based on data from the ongoing multicenter, 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 to not estimable). 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 enzyme inhibitors and other trials of rucaparib in the treatment of ovarian cancer. Deaths due to adverse events (AEs) occurred in 1.7% of patients, and 8% discontinued rucaparib because of 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 metastatic castrate-resistant prostate cancer 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.
KW - BRCA mutations
KW - Metastatic castrate-resistant prostate cancer
KW - Poly-(ADP-ribose) polymerase inhibitors
KW - Rucaparib
UR - http://www.scopus.com/inward/record.url?scp=85096652077&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096652077&partnerID=8YFLogxK
U2 - 10.1002/onco.13585
DO - 10.1002/onco.13585
M3 - Article
C2 - 33145877
AN - SCOPUS:85096652077
SN - 1083-7159
VL - 26
SP - 139
EP - 146
JO - Oncologist
JF - Oncologist
IS - 2
ER -