Two-year maintenance olaparib could reduce ovarian cancer recurrence risk

Two years of maintenance olaparib reduces recurrence risk in women with newly diagnosed advanced ovarian cancer with BRCA mutation (BRCAm), according to long-term results of the SOLO1* trial.

“The benefit derived from maintenance olaparib was sustained substantially beyond the end of treatment [where] median [progression-free survival (PFS)] was 56 months, whereas median treatment duration was only 25 months,” said Professor Michael Friedlander from the University of New South Wales Clinical School, Prince of Wales Hospital, Randwick, Australia, at ESMO Asia 2020.

Patients in SOLO1 had newly diagnosed, BRCAm high grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer and had demonstrated complete or partial response to first-line platinum-based chemotherapy. They were randomized to receive oral olaparib (300 mg BID; n=260) or placebo (n=131) for ≤2 years or until disease progression (median treatment duration 24.6 and 13.9 months, respectively).

At a median 4.8 and 5 years of follow-up in the olaparib and placebo arms, respectively, PFS was significantly improved in the olaparib arm (median 56.0 vs 13.8 months; hazard ratio [HR], 0.33, 95 percent confidence interval [CI], 0.25–0.43). [ESMO Asia 2020, abstract 234O]

Patients who had a complete response to platinum chemotherapy at baseline demonstrated a 63 percent reduction in recurrence or death with olaparib vs placebo (median recurrence-free survival [RFS] not reached vs 15.3 months; HR, 0.37, 95 percent CI, 0.27–0.52).

At 5 years, PFS and RFS were double in the olaparib vs the placebo arm (PFS: 48.3 percent vs 20.5 percent; RFS: 51.9 percent vs 21.8 percent).

Olaparib also fared better than placebo with regard to second PFS and time to second subsequent therapy in the overall population (HRs, 0.46 for both) and among those with complete response at baseline (HRs, 0.48 and 0.50, respectively).

This 5-year data follows up on the median 41-month primary analysis data which showed the PFS benefit of maintenance olaparib vs placebo in these patients (median not reached vs 13.8 months; HR, 0.30; p<0.001). [N Engl J Med 2018;379:2495-2505]

These primary findings led to the approval of olaparib as maintenance treatment in this population and has become a standard of care (SoC) in this setting, said Friedlander.

The safety profile was consistent with that observed in the primary analysis, with grade ≥3 adverse events (AEs) occurring in 40 and 19 percent of olaparib and placebo recipients, respectively, and serious AEs in 21 and 13 percent, respectively. AEs led to dose interruptions in 52 and 17 percent, respectively, dose reduction in 29 and 3 percent, and treatment discontinuation in 12 and 3 percent, respectively. There were no additional cases of acute myeloid leukaemia or myelodysplastic syndrome, with their incidence remaining at <1.5 percent. New primary malignancies occurred in 3 and 4 percent of olaparib and placebo recipients, respectively.

Clinically important findings

“[These findings are the result of] the longest duration of follow-up for any PARP inhibitor in the newly diagnosed advanced ovarian cancer setting,” said Friedlander.

Patients with newly diagnosed advanced ovarian cancer are at high risk of relapse, with a 5-year survival rate of 30–50 percent, he said.

“Treatment goals in the newly diagnosed setting include delay of recurrence and, for some patients, typically around 20 percent, the chance of cure,” he added. The newly diagnosed setting presents the best opportunity for increasing the likelihood of cure.

In SOLO1, >50 percent of patients who had complete response to platinum-based chemotherapy were relapse-free at 5 years. 

“These results provide further evidence to support the use of maintenance olaparib as a SoC for women with newly diagnosed advanced ovarian cancer and a BRCA mutation, and suggest the possibility of long-term remission, or even cure, for some patients,” he concluded.