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BRCAmut+ Metastatic Castration-Resistant Prostate Cancer (mCRPC)
SELECT INDICATION
The majority of adverse reactions and lab abnormalities were Grades 1 or 21
In a retrospective analysis of prostate cancer outcomes in patients with germline BRCA1 or BRCA2 mutations and noncarriers, BRCA carriers had a significantly more aggressive disease than noncarriers6
BRCA carriers were more likely to present
with a Gleason scorea ≥8, advanced stage disease, nodal involvement, and metastatic spread6
Mutations can occur in both the BRCA1 and BRCA2 genes, and both can lead to more aggressive prostate cancer6
Recommended for:
Consider for:
Recommended for:
Considered for:
Somatic testing may require repetition when prostate cancer progresses after treatment
BRCA mutations can be detected using tests that analyze tissue or circulating tumor DNA from blood1,8
Rubraca is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) has occurred in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28 day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA damaging agents. In TRITON2, MDS/AML was not observed in patients with mCRPC (n=209) regardless of homologous recombination deficiency (HRD) mutation.
Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.
Based on findings in genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential or who are pregnant to use effective methods of contraception during treatment and for 3 months following last dose of Rubraca. Advise male patients not to donate sperm during therapy and for 3 months following the last dose of Rubraca.
Most common adverse reactions in TRITON2 (≥ 20%; Grade 1-4) were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).
Co-administration of rucaparib can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring.
Please see full Prescribing Information for additional Important Safety Information.
References: 1. Rubraca. Prescribing Information. Clovis Oncology; 2022. 2. Abida W, Armenia J, Gopalan A, et al. Prospective genomic profiling of prostate cancer across disease states reveals germline and somatic alterations that may affect clinical decision making. JCO Precis Oncol. 2017;2017:PO.17.00029. 3. Lang SH, Swift SL, White H, Misso K, Kleijnen J, Quek RGW. A systematic review of the prevalence of DNA damage response gene mutations in prostate cancer, Int J Oncol. 2019;55(3):597-616. 4. Robson ME, Bradbury AR, Arun B, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2015;33(31):3660-3667. 5. Cheng HH, Sokolova AO, Schaeffer EM, Small EJ, Higano CS. Germline and somatic mutations in prostate cancer for the clinician. J Natl Compr Canc Netw. 2019;17(5):515-521. 6. Castro E, Goh C, Leongamornlert D, et al. Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localized prostate cancer. Eur Urol. 2015;68(2):186-193. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.4.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed August 18, 2022. To view the most recent and complete version of the guidelines, go to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 8. Foundation Medicine. FoundationOne Liquid technical specifications. https://assets.ctfassets.net/vhribv12lmne/3SPYAcbGdqAeMsOqMyKUog/4e0d771e88afc920dc1a6f0515e2ff83/F1L_TechnicalInformation_10.pdf. Accessed May 20, 2021. 9. Yap TA, Plummer R, Azad NS, Helleday T. The DNA damaging revolution: PARP inhibitors and beyond. AM Soc Clin Oncol Educ Book. 2019;39:185-195.
Rubraca is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) has occurred in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28 day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA damaging agents. In TRITON2, MDS/AML was not observed in patients with mCRPC (n=209) regardless of homologous recombination deficiency (HRD) mutation.
Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.
Based on findings in genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential or who are pregnant to use effective methods of contraception during treatment and for 3 months following last dose of Rubraca. Advise male patients not to donate sperm during therapy and for 3 months following the last dose of Rubraca.
Most common adverse reactions in TRITON2 (≥ 20%; Grade 1-4) were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).
Co-administration of rucaparib can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring.
Please see full Prescribing Information for additional Important Safety Information.
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