What is the treatment regimen for ovarian cancer patients using Rubraca (rucaparib)?

Rubraca (Rucaparib) Treatment Regimen for Ovarian Cancer

The recommended dose of Rubraca is 600 mg (two 300 mg tablets) taken orally twice daily with or without food, for a total daily dose of 1,200 mg, continued until disease progression or unacceptable toxicity. 1

FDA-Approved Indications

Rubraca has two distinct FDA-approved uses in ovarian cancer:

Maintenance Treatment Setting

• Indication: Maintenance treatment of adult patients with deleterious BRCA mutation (germline and/or somatic)-associated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy 2, 1
• Patient selection: Requires confirmed deleterious BRCA mutation (germline and/or somatic) 1
• Timing: Initiated after achieving CR or PR to platinum-based chemotherapy 2

Treatment Setting (Historical - Now Withdrawn)

• Previous indication: Treatment of patients with deleterious BRCA mutation-associated ovarian cancer who had been treated with ≥2 prior lines of chemotherapy 2, 3
• Important update: This treatment indication was voluntarily withdrawn in June 2022 due to lack of overall survival benefit in the ARIEL-4 trial 2
• Current status: Rucaparib monotherapy for recurrent disease is now Category 3 (Other Recommended regimens) rather than preferred therapy 2

Dosing Administration Details

Standard Dosing

• Starting dose: 600 mg twice daily (two 300 mg tablets) 1
• Total daily dose: 1,200 mg 1
• Food interaction: Can be taken with or without food (high-fat meals cause weak increases in exposure but not clinically significant) 1, 4
• Duration: Continue until disease progression or unacceptable toxicity 1

Dose Modifications for Adverse Reactions

The following dose reduction schedule should be followed for managing adverse reactions 1:

• 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)

Missed or Vomited Doses

• If a dose is missed, take the next dose at its scheduled time (do not double up) 1
• Vomited doses should not be replaced 1

Patient Selection Requirements

BRCA Mutation Testing

• Required: Confirmed deleterious BRCA mutation (germline and/or somatic) 1
• Testing method: FDA-approved companion diagnostic (FoundationFocus CDx BRCA test was the first next-generation sequencing-based companion diagnostic approved) 3
• Important note: An FDA-approved test for detecting deleterious germline and/or somatic BRCA mutations in ovarian cancer is required for patient selection 1

Disease Status Requirements

• Must be in complete or partial response to platinum-based chemotherapy for maintenance indication 2, 1
• Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer 2, 1

Clinical Efficacy Data

Maintenance Setting (ARIEL3 Trial)

• Rucaparib significantly improved progression-free survival in platinum-sensitive ovarian cancer patients in complete or partial response to platinum-based chemotherapy 2, 5
• Greatest benefit observed in patients with BRCA mutations 2

Treatment Setting (Historical Data)

• In the combined analysis of 106 BRCA-mutated ovarian cancer patients treated with ≥2 prior chemotherapies, investigator-assessed objective response rate was 54% (95% CI: 44-64%) 3
• Median duration of response was 9.2 months (95% CI: 6.6-11.7) 3
• In Study 10 final results, ORR was 59.3% (95% CI: 45.0-72.4%) in heavily pretreated patients 6

Safety Profile and Common Adverse Events

Most Common Adverse Reactions (≥20%)

The following adverse events occur frequently and require monitoring 1, 3:

• Nausea
• Fatigue
• Vomiting
• Anemia
• Abdominal pain
• Dysgeusia (taste changes)
• Constipation
• Decreased appetite
• Diarrhea
• Thrombocytopenia
• Dyspnea

Timing of Adverse Events

• Nonhematological TEAEs: Typically occur early (<56 days) 6
• Hematological TEAEs: Occur later (53-84 days) 6
• Duration of grade ≥3 TEAEs: Median ≤13 days 6
• Steady state: Achieved after continuous twice-daily dosing for one week 4

Management Strategy

• Adverse reactions are generally manageable with dose interruption, dose reduction, and/or supportive care 1, 5, 6
• Consider dose modifications per the reduction schedule outlined above 1

Important Clinical Context and Caveats

Recent FDA and Guideline Changes

Critical update: As of 2022-2024, the landscape for PARP inhibitor monotherapy in recurrent ovarian cancer has changed significantly 2:

• Rucaparib's treatment indication (≥2 prior chemotherapies) was voluntarily withdrawn in June 2022 due to lack of OS benefit in ARIEL-4 2
• NCCN downgraded rucaparib monotherapy for recurrent disease from Category 2A Preferred to Category 3 Other Recommended 2
• The maintenance indication after recurrence therapy was restricted to patients with germline or somatic BRCA mutations only (no longer includes HRD-positive/BRCA wild-type) 2

Current Appropriate Use

• Preferred use: Maintenance therapy in BRCA-mutated patients responding to platinum-based chemotherapy 2
• Treatment setting: Now Category 3; consider only when other options exhausted 2
• PARP inhibitor-naïve patients: Should preferentially receive PARP inhibitors in the first-line maintenance setting where benefit is greatest 2

Pharmacokinetic Considerations

• Moderate oral bioavailability with accumulation after repeated administration 4
• No dose adjustments needed for mild-to-moderate hepatic or renal impairment 4
• Moderately inhibits CYP1A2 and weakly inhibits CYP3As, CYP2C9, and CYP2C19 4
• Monitor for drug interactions with substrates of these enzymes 4