Rubraca® (rucaparib) tablets

Now Approved

RUBRACA: A NEXT STEP
FOR PATIENTS WITH
BRCAmut+ mCRPC

FOLLOWING AR-TARGETED THERAPY AND CHEMOTHERAPY1

A first-in-class, oral therapy for a genetically defined population of patients with BRCAmut+ mCRPC1


A prospective clinical trial of patients with BRCAmut+ mCRPC1,2

  • TRITON2 (a multicenter, single-arm, phase 2 clinical trial) enrolled 209 patients with HRD+ mCRPC who had been previously treated with AR-directed therapy and taxane-based chemotherapy1
  • Patients received Rubraca 600 mg orally, twice daily until disease progression or unacceptable toxicity, and also received concomitant GnRH analog or had prior bilateral orchiectomy1
  • 115 patients with BRCAmut+ mCRPC were evaluated for safety and efficacy, of which 62 patients had measurable disease at baseline by IRR. Major efficacy outcomes were confirmed ORR by IRR using modified RECIST v1.1/PCWG3 criteria and DOR. PSA response was also evaluated1,2

Demonstrated Efficacy with Rubraca—44% of Patients had a Response1*

Confirmed objective response rate (ORR): primary endpoint1

IRR-assessed response (N=62)

  • ORR was defined per modified RECIST v1.1 criteria and with no confirmed bone progression per PCWG31
  • The ORR by IRR was similar in patients with germline vs somatic BRCA mutation1
  • Of those that responded on Rubraca, the majority (70%) achieved an initial response by the first follow-up scan (week 8 visit)2

Demonstrated durability with Rubraca—some responses remained ongoing at 2 years1

Duration of response (DOR): secondary endpoint1

IRR-assessed DOR1

Median IRR-assessed DOR was not evaluable at data cut-off
(95% CI: 6.4, NE)

Responses ranged from 1.7 months to ongoing at 24 months

  • 15 of the 27 (56%) patients with a confirmed objective response had a DOR of ≥6 months1
  • Median follow-up of 17.3 months2
  • Treatment with Rubraca was still ongoing in 26% (16/62) of patients at the time of data cut-off2

Confirmed PSA response with Rubraca: secondary endpoint

Confirmed PSA response (N=115)2

55%

More than half (55%; 95% CI: 45.2, 64.1) of patients with measurable or nonmeasurable disease had a confirmed PSA response while on Rubraca


An oral monotherapy you can prescribe with confidence at the start

The recommended starting dose for Rubraca is 600 mg twice daily, with or without food1

  • Select patients for treatment with Rubraca based on the presence of a deleterious BRCA mutation (germline and/or somatic)1
  • Patients should also receive a GnRH analog concurrently or should have had a bilateral orchiectomy1
  • Continue until disease progression or unacceptable toxicity1

Rubraca is available in 3 strengths to help provide dosing flexibility when needed1

Dose
Reduction
Dose Tablets
First dose reduction 500 mg twice daily
(two 250-mg tablets)
Second dose reduction 400 mg twice daily
(two 200-mg tablets)
Third dose reduction 300 mg twice daily
(one 300-mg tablet)


Tablets not shown actual size.

>90% of patients were able to stay on Rubraca without discontinuing therapy due to adverse reactions1

The discontinuation rate for Rubraca was 8%, with none of the adverse reactions leading to discontinuation of Rubraca occurring in more than one patient.1‡

Dose Modifications (N=115)1,2

Dose modification Rate (%) Adverse reactions requiring dose
modification in >5% of patients
Dose interruption 57 Anemia (21.7%), thrombocytopenia (13.9%), asthenia/fatigue (9.6%), nausea (7.0%), vomiting (6.1%), neutropenia (6.1%)
Dose reduction 41 Anemia (14%), asthenia/fatigue (10%), thrombocytopenia (7%), nausea (6%)
Dose modification Rate (%)
Dose interruption 57
Adverse reactions requiring dose
modification in >5% of patients
Anemia (21.7%), thrombocytopenia (13.9%), asthenia/fatigue (9.6%), nausea (7.0%), vomiting (6.1%), neutropenia (6.1%)
Dose modification Rate (%)
Dose reduction 41
Adverse reactions requiring dose
modification in >5% of patients
Anemia (14%), asthenia/fatigue (10%), thrombocytopenia (7%), nausea (6%)

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend genetic testing for BRCA1/2 mutation in appropriate prostate cancer patients3

  • BRCA mutations can be detected using tests that analyze tissue or circulating tumor DNA from blood1,4

Take Action: Test your patients with mCRPC for BRCA mutations today and treat eligible patients with Rubraca

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*ORR and DOR were assessed by blinded IRR and the investigator according to modified RECIST version 1.1/PCWG3 criteria.
PSA response defined as the proportion of patients with a ≥50% decrease from baseline confirmed by a second consecutive measurement at least 3 weeks later; PSA measurements performed by local laboratory.
ECG QT prolonged, acute respiratory distress syndrome, anemia, balance disorder, cardiac failure, decreased appetite/fatigue/weight decreased, leukopenia/neutropenia, ALT/AST increased, and pneumonia.
ALT=alanine aminotransferase; AR therapy=androgen receptor-directed therapy; AST=aspartate aminotransferase; BRCAmut+ mCRPC=breast cancer susceptibility gene-positive metastatic castration-resistant prostate cancer; ECG=electrocardiogram; GnRH=gonadotropin-releasing hormone agonist; HRD=homologous recombination deficiency; IRR=independent radiologic review; PCWG3=Prostate Cancer Working Group 3; PSA=prostate-specific antigen; QT=an electrocardiogram representation of ventricular depolarization and repolarization; RECIST=Response Evaluation Criteria in Solid Tumors.


INDICATION

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. 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.

SELECT IMPORTANT SAFETY INFORMATION

Read full ISI

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]. Boulder, CO: Clovis Oncology. 2. Data on file. Clovis Oncology; Boulder, CO. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed March 19, 2020. To view the most recent and complete version of the guideline, go online 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. 4. Foundation Medicine. FoundationOneLiquid technical specifications. https://assets.ctfassets.net/vhribv12lmne/3SPYAcbGdqAeMsOqMyKUog/4e0d771e88afc920dc1a6f0515e2ff83/F1L_TechnicalInformation_10.pdf. Accessed March 18, 2020.

 

INDICATION

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. 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.

SELECT IMPORTANT SAFETY INFORMATION

Read full ISI

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.