Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and BRCA mutation (SOLO1 / GOG 3004): 5-year follow-up of a randomized, double-blind, controlled phase 3 trial by placebo

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Background

There is a great unmet need for treatment regimens that increase the chances of long-term remission and possibly cure for women with newly diagnosed advanced ovarian cancer. In the primary analysis of SOLO1 / GOG 3004, the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib significantly improved progression-free survival compared to placebo in patients with BRCA mutation; median progression-free survival was not reached. Here we report an updated post-hoc analysis of the progression-free survival of SOLO1, after 5 years of follow-up.

Methods

SOLO1 was a randomized, double-blind, placebo-controlled phase 3 trial conducted at 118 centers in 15 countries, which included patients aged 18 years or older with an Eastern Cooperative Oncology Group performance index of 0 -1 and with BRCA-new diagnosed, advanced, high grade mutated serous or endometrioid ovarian cancer with complete or partial clinical response after platinum-based chemotherapy. Patients were randomized (2: 1) via an online or interactive voice response system to receive olaparib (300 mg twice daily) or oral placebo tablets as maintenance monotherapy for a period of up to go up to 2 years; randomization was in blocks and was stratified according to clinical response after platinum-based chemotherapy. Patients, treatment providers, and data reviewers were masked for group assignment. The primary endpoint was progression-free survival as assessed by the investigator. Efficacy is reported in the intention-to-treat population and safety in patients who have received at least one dose of treatment. The data cut-off date for this updated post-hoc analysis was March 5, 2020. This trial is registered with
ClinicalTrials.gov (NCT01844986) and is ongoing but closed to new participants.

Results

Between September 3, 2013 and March 6, 2015, 260 patients were randomized to receive olaparib and 131 to placebo. The median duration of treatment was 24.6 months (IQR 11.2-24.9) in the olaparib group and 13.9 months (8.0-24.8) in the placebo group; the median follow-up was 4.8 years (2.8–5.3) in the olaparib group and 5.0 years (2.6–5.3) in the placebo group. In this post-hoc analysis, the median progression-free survival was 56.0 months (95% CI 41.9 – not achieved) with olaparib versus 13.8 months (11.1–18.2) with placebo (hazard ratio 0.33 [95% CI 0·25–0·43]). The most common grade 3-4 adverse events were anemia (57 [22%] of 260 patients receiving olaparib vs of them [2%] out of 130 receiving placebo) and neutropenia (22 [8%] vs six [5%]), and serious adverse events occurred in 55 (21%) of 260 patients in the olaparib group and 17 (13%) of 130 patients in the placebo group. No treatment-related adverse events occurring during study treatment or up to 30 days after discontinuation were reported to result in death. No additional cases of myelodysplastic syndrome or acute myeloid leukemia have been reported since the primary data cut-off date, including after the 30-day safety follow-up period.

Interpretation

For patients with newly diagnosed advanced ovarian cancer and BRCA mutation, after, to our knowledge, the longest follow-up for any randomized controlled trial of a PARP inhibitor in this setting, the benefit from 2-year maintenance treatment with olaparib was maintained at – beyond the end of treatment, prolonging the median progression-free survival beyond 4.5 years. These results support the use of maintenance olaparib as the standard of care in this setting.

Funding

AstraZeneca; Merck Sharpe & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA.


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