What is the duration of maintenance olaparib (Lynparza) therapy in ovarian cancer?

From the Guidelines

Maintenance olaparib is typically given for 2 years in patients with ovarian cancer who have responded to first-line platinum-based chemotherapy, particularly those with BRCA mutations or homologous recombination deficiency (HRD). This recommendation is based on the most recent and highest quality study, the NCCN guidelines 1, which examined the efficacy of PARP inhibitors as maintenance regimens post primary therapy. The SOLO-1 trial, included in the guidelines, investigated 2 years of maintenance olaparib in patients with newly diagnosed advanced ovarian cancer harboring germline or somatic BRCA1/2 mutations, and demonstrated a remarkable improvement in progression-free survival (PFS) 1.

The standard dose of olaparib is 300mg (two 150mg tablets) taken twice daily. This maintenance therapy significantly improves progression-free survival by inhibiting poly(ADP-ribose) polymerase (PARP), which prevents cancer cells from repairing DNA damage, leading to cancer cell death. This is especially effective in tumors with defects in homologous recombination repair pathways, such as those with BRCA mutations. Patients should be monitored for common side effects including fatigue, nausea, anemia, and neutropenia. Regular blood counts should be performed, and dose adjustments may be necessary based on tolerability. Patients should take the medication with or without food and avoid grapefruit products during treatment.

Some key points to consider when prescribing maintenance olaparib include:

• The patient's BRCA mutation status or homologous recombination deficiency (HRD) status
• The patient's response to first-line platinum-based chemotherapy
• The potential for improved progression-free survival with olaparib maintenance therapy
• The need for regular monitoring of side effects and dose adjustments as necessary
• The importance of patient education on proper medication administration and potential interactions with other medications or foods.

Additionally, other guidelines, such as the ESMO clinical practice guideline 1, also recommend maintenance treatment with olaparib for 2 years in patients with BRCA1/2-mutated tumors, with a score of 4 on the ESMO-MCBS v1.1 scale, indicating a high level of clinical benefit.

From the Research

Maintenance Olaparib in Ovarian Cancer

• The duration of maintenance olaparib in ovarian cancer is not explicitly stated in the provided studies, but the treatment is continued until disease progression or unacceptable toxicity occurs 2, 3, 4, 5, 6.
• In the SOLO1 trial, patients received olaparib tablets (300 mg twice daily) or placebo for a median follow-up of 41 months 2.
• In the Study 19 trial, patients received maintenance monotherapy with olaparib capsules (400 mg bid) or placebo, with 32 patients (24%) receiving maintenance olaparib for over 2 years and 15 (11%) for over 6 years 5.
• The olaparib tablet formulation has improved bioavailability, reducing pill burden and offering a more convenient dosage regimen compared to the earlier capsule formulation 6.
• Maintenance treatment with olaparib is generally well-tolerated, with most adverse events being mild or moderate in severity 2, 3, 4, 5, 6.

Key Findings

• Maintenance olaparib has been shown to significantly prolong progression-free survival (PFS) in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer, regardless of BRCA mutation status 2, 5, 6.
• The use of maintenance therapy with olaparib provided a substantial benefit with regard to PFS among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, with a 70% lower risk of disease progression or death with olaparib than with placebo 2.
• Proper management of olaparib-related adverse events is important for the improvement of quality of life and maximization of the efficacy of maintenance therapy 3.

Adverse Events

• Adverse events associated with maintenance olaparib include renal function deterioration, which is likely to occur during maintenance treatment, and careful administration is important in platinum-sensitive advanced ovarian cancer 4.
• The incidence of discontinuations due to adverse events was low (6%) in the Study 19 trial 5.