Maintenance olaparib for patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation: 5-year follow-up from SOLO1

Abstract

<h3>Objectives:</h3> Newly diagnosed advanced ovarian cancer patients (pts) are at high risk of relapse and 5-year survival is 30–50%. Delay of recurrence, prolonged survival and, for some pts, increased chance of cure are goals of treatment in this setting. In SOLO1 (NCT01844986; GOG-3004) pts with advanced ovarian cancer and a <i>BRCA1</i> and/or <i>BRCA2</i> mutation (BRCAm) who were in response after first-line platinum-based chemotherapy derived significant progression-free survival (PFS) benefit from maintenance olaparib vs placebo (median 41 months follow-up; median not reached vs 13.8 months; hazard ratio 0.30; <i>P</i><.001; Moore <i>et al. NEJM</i> 2018). We report analyses after 5-years of follow-up (data cut-off [DCO]: March 5, 2020), performed to assess the long-term efficacy and tolerability of maintenance olaparib for newly diagnosed advanced ovarian cancer. <h3>Methods:</h3> Pts received maintenance olaparib (tablets; 300 mg bid) or placebo for up to 2 years or until progression. PFS and recurrence-free survival (RFS) were investigator-assessed by modified RECIST v1.1. An exploratory subgroup analysis of PFS in higher-risk (stage IV disease, stage III disease with residual disease following primary debulking surgery, inoperable stage III disease, or stage III disease and had undergone interval surgery) and lower-risk (stage III disease without residual disease following primary debulking surgery) pts was carried out. For pts in complete response at baseline, RFS was defined <i>post hoc</i> as time from randomization to disease recurrence (new lesions by imaging) or death. <h3>Results:</h3> A total of 260 pts were randomized to olaparib; 131 to placebo (median treatment duration 24.6 vs 13.9 months, respectively). After a median of 4.8 and 5.0 years of follow-up, median PFS was 56 vs 14 months in the olaparib and placebo arms, respectively (Table). In the higher-risk subgroup 42% of olaparib-arm vs 17% of placebo-arm pts were free from progression at 5 years; in the lower-risk subgroup 56% vs 25% of pts, respectively, were progression free at this time point. Among pts in complete response at baseline, risk of disease recurrence or death was reduced by 63%. The safety profile of olaparib was consistent with previous observations. No new cases of myelodysplastic syndrome or acute myeloid leukaemia were reported (previous DCO: olaparib, 3/260 [1%]; placebo, 0/130), and incidence of new primary malignancies remained balanced between arms (olaparib, 7/260 [3%]; placebo, 5/130 [4%]). <h3>Conclusions:</h3> For pts with a <i>BRCA</i>m and newly diagnosed advanced ovarian cancer, the benefit derived from 2 years of maintenance olaparib was sustained beyond the end of treatment, and after 5 years, almost half of pts were progression free vs 20% with placebo. This benefit was consistent across higher- and lower-risk pts. Over 50% of pts in complete response after first-line platinum-based chemotherapy remained free from relapse 5 years after randomization. A total of 5 years of follow-up is the longest for any PARP inhibitor in this setting and no new safety signals were observed.