Rubraca has an established
and Manageable safety Profile

The Majority of Adverse Reactions and Lab Abnormalities
Were Mild to Moderate (Grades 1 or 2)2

Adverse reactions reported in ≥20% of patients with BRCA+ mCRPC (N=115)2†

Grades 1-4

Grades 3-4

Asthenia/
Fatigue

62
9

Nausea

52
3

Anemia

43
25

ALT/AST
increased

33
5

Decreased
appetite

28
2

Rash

27
2

Constipation

27
1

Thrombocytopenia§

25
10

Vomiting

22
1

Diarrhea

20
0

0

20

40

60

80

100

Adverse reactions (%)

Incidence (%)

Laboratory abnormalities in ≥35% (Grades 1-4) and ≥2% (Grades 3-4) worsening
from baseline in patients with BRCA+ mCRPC2||¶

Grades 1-4

Grades 3-4

Increase in ALT**

69
5

Decrease in
leukocytes

69
5

Decrease in
phosphate

68
15

Decrease in absolute
neutrophil count

62
10

Decrease in
hemoglobin

59
25

Increase in alkaline
phosphatase

44
2

Increase in
creatinine

43
2

Decrease in
lymphocytes

42
17

Increase in
triglycerides

42
5

Decrease in
platelets

40
10

Decrease in
sodium

38
3

0

20

40

60

80

100

Adverse reactions (%)

Incidence (%)

92% of Patients Were Able to Stay on Rubraca Without Discontinuing Therapy Due to Adverse Reactions2

Father and son together

Dose Interruption & Reduction

Dose
modification
(N=115)1,2

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%)

Recommendations for monitoring2

Bar chart and line chart icon

At Baseline

  • Monitor complete blood counts for cytopenia at baseline, and monthly thereafter for clinically significant changes during treatment
  • No requirement for weekly monitoring for hematologic adverse events
hematologic toxicity icon

Prolonged
Hematologic Toxicities

  • For toxicities >4 weeks, dose interruptions or reductions are recommended; monitor blood counts weekly until recovery
  • *
    For a PSA50 and PSA90 response, respectively, the proportion of patients with a ≥50% decrease or a ≥90% decrease from baseline confirmed by a second consecutive measurement at least 3 weeks later; PSA measurements performed by local laboratory.
  • National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
  • Includes blister, blood blister, dermatitis, dermatitis contact, eczema, genital rash, palmar-plantar erythrodysaesthesia syndrome, photosensitivity reaction, psoriasis, rash, rash maculo-papular, rash pruritic, skin exfoliation, skin lesion, urticaria.
  • §
    Includes platelet count decreased.
  • ||
    Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available for 111 to 115 patients.
  • NCI CTCAE version 5.0; decrease in phosphate is graded using NCI CTCAE Version 4.03.
  • **
    Grade 3-4 ALT or AST elevation led to drug interruption in 4 patients, of which 1 had dose reduction upon rechallenge.
  • ††
    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; AST=aspartate aminotransferase; ECG=electrocardiogram; QT=an electrocardiogram representation of ventricular depolarization and repolarization.

INDICATIONS

Rubraca is indicated:

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.

SELECT IMPORTANT SAFETY INFORMATION

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.

Reference: 1. Data on file. Clovis Oncology; Boulder, CO. 2. Rubraca [prescribing information]. Boulder, CO; Clovis Oncology.

INDICATIONS

Rubraca is indicated:

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.

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.

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