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Maintenance Olaparib in Newly Diagnosed Advanced Ovarian Cancer

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Key Points

  • Olaparib significantly prolonged progression-free survival vs placebo.
  • Progression-free survival at 3 years was 60% vs 27%.

As reported in The New England Journal of Medicine by Moore et al, the phase III SOLO-1 trial has shown that maintenance with olaparib, following complete or partial response to platinum-based chemotherapy, significantly prolonged progression-free survival vs placebo in newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with a BRCA1BRCA2, or BRCA1/2 mutation. The trial supported the recent U.S. Food and Drug Administration approval of olaparib in this setting.

In the double-blind international trial, 391 patients who had complete or partial clinical response after platinum-based chemotherapy were randomly assigned 2:1 between September 2013 and March 2015 to receive oral olaparib at 300 mg twice daily (n = 260) or placebo (n = 131). Treatment was continued until disease progression or unacceptable toxicity or for up to 2 years; patients with no evidence of disease at 2 years stopped receiving study treatment, whereas those with partial response at 2 years were permitted to continue receiving treatment in blinded fashion. The primary endpoint was investigator-assessed progression-free survival.

Progression-Free Survival

Median follow-up was 41 months. The Kaplan-Meier estimate of progression-free survival at 3 years was 60% in the olaparib group vs 27% in the placebo group (hazard ratio [HR] = 0.30, P < .001). Median progression-free survival was not reached in the olaparib group vs 13.8 months in the placebo group. Progression-free survival was 88% vs 51% at 1 year and 74% vs 35% at 2 years. On blinded independent central review, progression-free survival at 3 years was 69% vs 35% (HR = 0.28, P < .001). All subgroup analyses favored olaparib, including subgroups for the stratification factors of complete response (HR = 0.35, 95% confidence interval [CI] = 0.26–0.49) and partial response (HR = 0.19, 95% CI = 0.11–0.34) after prior platinum-containing chemotherapy.

Overall survival data were immature at the time of analysis (21% data maturity). Overall survival at 3 years was 84% vs 80% (HR = 0.95, 95% CI = 0.60–1.53). Median time to the first subsequent therapy or death was 51.8 months vs 15.1 months (HR = 0.30, 95% CI = 0.22–0.40).

Adverse Events

The most common adverse events of any grade in the olaparib group were nausea (77% vs 38% in placebo group), fatigue/asthenia (63% vs 42%), vomiting (40% vs 15%), anemia (39% vs 10%), and diarrhea (34% vs 25%). Grade 3 or 4 adverse events occurred in 39% vs 18% of patients, with the most common in the olaparib group being anemia (22%) and neutropenia (9%). Serious adverse events occurred in 21% vs 12% of patients, with the most common in the olaparib group being anemia (7%). No adverse events resulted in death.

The investigators concluded,“The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression-free survival 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.”

Disclosure: The study was funded by AstraZeneca and Merck. The study authors’ full disclosures can be found at nejm.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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