From the Guidelines
The recommended duration of adjuvant olaparib therapy for patients with BRCA1-mutated ovarian cancer is 2 years (24 months) of continuous treatment. This recommendation is based on the most recent and highest quality study, the NCCN guidelines 1, which suggests that olaparib maintenance therapy for up to 24 months has shown significant improvement in progression-free survival (PFS) in patients with BRCA1/2 mutations.
Key Points
- Olaparib is typically prescribed at a dose of 300 mg (two 150 mg tablets) taken twice daily for a total daily dose of 600 mg 1.
- This maintenance therapy should be initiated after completion of first-line platinum-based chemotherapy in patients who have demonstrated a complete or partial response to that initial treatment 1.
- Patients should continue therapy for the full 2-year period unless they experience disease progression or unacceptable toxicity that cannot be managed with dose reductions or temporary interruptions 1.
- The 2-year duration was established based on clinical trials, such as the SOLO-1 trial, showing significant improvement in PFS with this treatment duration 1.
Rationale
The rationale behind olaparib's effectiveness is its mechanism as a PARP (poly ADP-ribose polymerase) inhibitor, which exploits the defective DNA repair pathway in BRCA-mutated cancer cells, leading to synthetic lethality and cancer cell death 1.
Monitoring
Regular monitoring during treatment should include complete blood counts monthly for the first year and periodically thereafter to watch for potential hematologic toxicities 1.
Benefits
The benefits of olaparib maintenance therapy include a significant improvement in PFS, with a rate of freedom from disease progression and death at 3 years of 69% in those receiving olaparib compared with 35% in those receiving placebo 1. Additionally, longer follow-up at 7 years showed that 67% of patients treated with olaparib compared with 46% of patients treated with placebo were still alive 1.
From the Research
Adjuvant Therapy Duration for Ovarian Cancer with BRCA1 Mutation
The duration of olaparib (Lynparza) adjuvant therapy for ovarian cancer with a BRCA1 mutation is as follows:
- Maintenance therapy with olaparib tablets was given for up to 2 years in the SOLO1 trial 2
- The median treatment duration was 24.6 months in the olaparib group and 13.9 months in the placebo group in the SOLO1 trial 2
- In the SOLO2/ENGOT-Ov21 trial, the median follow-up was 65.7 months with olaparib and 64.5 months with placebo 3
Key Findings
- The SOLO1 trial showed that maintenance olaparib provided a significant progression-free survival benefit in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation 2
- The SOLO2/ENGOT-Ov21 trial demonstrated that olaparib tablets as maintenance therapy significantly improved progression-free survival in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation 4, 3
- The most common adverse events associated with olaparib were anemia, neutropenia, and fatigue/asthenia, which were generally manageable with supportive treatment and/or dose modification 2, 5
Study Details
- The SOLO1 trial was a randomized, double-blind, placebo-controlled, phase 3 trial that enrolled 391 patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation 2
- The SOLO2/ENGOT-Ov21 trial was a double-blind, randomized, placebo-controlled, phase 3 trial that enrolled 295 patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation 4, 3