Benefit of Maintenance Therapy with Olaparib in Newly Diagnosed Advanced Ovarian Cancer

Introduction

The diagnosis of ovarian cancer is unfortunately often made at an advanced stage. In most women with advanced ovarian cancer, despite standard surgical treatment and platinum-based chemotherapy, relapse of the disease occurred within 3 years of treatment, significantly worsening their prognosis. Despite the strong position of olaparib, an oral PARP (poly-ADP-ribose polymerase) inhibitor, in the maintenance treatment of relapsed disease, its potential benefit for patients with newly diagnosed cancer was unclear. The breakthrough in this regard was the SOLO-1 study published in December 2018 in The New England Journal of Medicine.

Study Methodology

This was an international randomized phase III clinical trial. The study population consisted of patients with advanced (corresponding to FIGO stage III or IV) high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (or their combination) with a confirmed BRCA1, BRCA2 mutation, or both types of mutation, who completely or partially responded to platinum-based chemotherapy.

Patients were randomized in a 2:1 ratio to the olaparib arm (in tablet form at a dose of 300 mg twice daily) or the placebo arm. The study intervention continued until objective disease progression (evaluated by the investigator). Patients showing a partial response after 2 years of therapy could continue in the blinded study regimen, while therapy was discontinued in patients without signs of disease. The primary endpoint was progression-free survival (PFS).

Results

After a median follow-up of 41 months, the risk of disease progression or death (assessed by investigators) was 70% lower in the olaparib group than in the placebo group (hazard ratio [HR] 0.30; 95% confidence interval [CI] 0.23–0.41; p < 0.001). The median PFS for patients in the placebo arm was 13.8 months, while the median PFS was not reached in the olaparib arm. After 3 years of follow-up, 60% of patients treated with olaparib were disease-free compared to only 27% of those in the placebo arm.

Adverse events were mild (grade 1 and 2) and consistent with the known safety profile of olaparib – the most common were nausea (in 77% of cases), fatigue, and vomiting. The most common serious adverse events (grade 3 and above) were anemia and neutropenia.

Conclusion

Maintenance therapy with olaparib significantly reduced the risk of disease progression (by 70%) in patients with newly diagnosed ovarian, fallopian tube, or primary peritoneal cancer with germline and/or somatic BRCA1/2 mutation after complete or partial response to platinum-based chemotherapy. The SOLO-1 study provided the basis for the approval of olaparib as first-line treatment in this indication, which occurred in the European Union in June 2019. Olaparib has become the only PARP-1 inhibitor approved in the EU for this indication to date.

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Source: Moore K., Colombo N., Scambia G. et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018; 379 (26): 2495−2505, doi: 10.1056/NEJMoa1810858.