What is the recommended duration of olaparib maintenance therapy for a patient with high‑grade serous ovarian cancer and a BRCA mutation who has responded to platinum‑based chemotherapy?

Olaparib Maintenance Therapy Duration in BRCA-Mutated Ovarian Cancer

For patients with high-grade serous ovarian cancer and BRCA mutations who have responded to platinum-based chemotherapy, olaparib maintenance therapy should be continued for 2 years (24 months) or until disease progression or unacceptable toxicity, whichever occurs first. 1

Standard Treatment Duration

• The recommended duration is 2 years (24 months) of continuous maintenance therapy based on the SOLO-1 trial protocol, which demonstrated a 70% reduction in risk of progression or death (HR 0.30; 95% CI 0.23-0.41) 1

• The standard dosing is olaparib 300 mg (two 150 mg tablets) orally twice daily, taken continuously until disease progression or unacceptable toxicity 1

• In the PAOLA-1 trial combining olaparib with bevacizumab, olaparib was administered for up to 24 months while bevacizumab was given for 15 months total 1

Evidence Supporting 2-Year Duration

• The SOLO-1 trial, which established olaparib as first-line maintenance therapy, used a 2-year treatment protocol and showed unprecedented progression-free survival benefit with median PFS not reached after 41 months of follow-up versus 13.8 months for placebo 1

• This represents a Category 1 recommendation from NCCN for patients with germline BRCA1/2 mutations and Category 2A for somatic BRCA1/2 mutations 1

• The time to first subsequent therapy was dramatically extended to 51.8 months with olaparib versus 15.1 months with placebo (HR 0.30; 95% CI 0.22-0.40) 1

Long-Term Treatment Experience

• Real-world data demonstrates that 24% of patients continued olaparib maintenance for over 2 years, with 11% continuing for over 6 years without new safety signals 2

• Long-term treatment showed no new tolerability concerns, with adverse events remaining generally low grade and discontinuation rates due to adverse events remaining low at 6% 2

• Patients who continued beyond 2 years maintained clinical benefit, suggesting that treatment can be extended beyond the standard 24-month duration if disease remains stable and treatment is well-tolerated 2

Treatment Continuation Beyond 2 Years

• While the standard protocol specifies 2 years, treatment should continue until disease progression if the patient is tolerating therapy well 1

• The primary stopping criteria are:

  • Radiologic disease progression per RECIST 1.1 criteria 3
  • Unacceptable toxicity despite dose reductions and supportive care 1
  • Patient decision to discontinue 3

• For patients completing 2 years without progression, clinical judgment should guide whether to continue therapy, considering individual response, tolerability, and patient preference 2

Recurrent Disease Setting

• In the platinum-sensitive recurrent setting (Study 19, SOLO-2), olaparib maintenance was continued until disease progression without a predetermined time limit 3, 2

• Median PFS in recurrent disease was 8.4-19.3 months depending on the number of prior lines of therapy, with some patients continuing treatment for over 6 years 3, 2, 4

• The ORZORA trial in platinum-sensitive recurrent disease showed median PFS of 18.0 months for BRCA-mutated patients, with treatment continuing until progression 4

Monitoring During Maintenance

• CA-125 monitoring should be performed regularly, though isolated CA-125 elevation without radiologic progression does not mandate treatment discontinuation 1

• Radiologic assessment should occur every 12 weeks during the first year, then as clinically indicated 3

• Hematologic monitoring is essential, with complete blood counts recommended monthly during the first year, then periodically thereafter, as anemia (17% any grade, 6-13.6% grade ≥3) is the most common hematologic toxicity 1, 5, 3

Dose Modifications

• If toxicity occurs, dose reduction to 250 mg twice daily, then 200 mg twice daily is recommended before discontinuation 1

• Approximately 21% of patients in real-world settings required dose reduction, most commonly for anemia, without compromising efficacy 6

• Treatment interruptions for toxicity management are acceptable and do not require permanent discontinuation 1

Critical Considerations

• The 2-year duration applies specifically to the first-line maintenance setting after primary platinum-based chemotherapy 1

• For recurrent disease, no maximum duration is specified—treatment continues until progression 3, 2

• Patients must have achieved complete or partial response to platinum-based chemotherapy before initiating maintenance therapy 1

• The remarkable PFS benefit seen with olaparib (70% risk reduction) far exceeds that of bevacizumab maintenance (approximately 30% improvement), making the 2-year commitment worthwhile despite potential toxicities 1