Two years of treatment with the PARP inhibitor olaparib had been shown to improve overall survival (OS) after 7 years of follow-up in women with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 mutation.
The international SOLO1 trial randomised patients to either olaparib (300 mg twice daily) or placebo tablets as maintenance monotherapy following completion of platinum-based chemotherapy.
The study has previously reported a 70% lower risk of disease progression or death after 41 months of follow-up, and improved progression-free survival (PFS) (56·0 v 13·8 months; HR 0·33) after the 5-year follow-up.
In the latest results, the study found 67.0% of olaparib patients versus 46.5% of placebo patients were alive at 7 years.
“The median OS was not reached (95% CI, not reached to not reached) in the olaparib group compared with 75.2 months (95% CI, 65.4 to not reached) in the placebo group, with an HR of 0.55 (95% CI, 0.40 to 0.76; P = .0004 [P < .0001 required to declare statistical significance],” it said.
“Although not reaching the threshold for statistical significance, we consider the OS benefit shown in this 7-year descriptive analysis to be clinically meaningful.”
The study also found the time from random assignment to first subsequent therapy or death was 64.0 months with olaparib compared with 15.1 months with placebo (HR 0.37).
Time from random assignment to second subsequent therapy or death was 93.2 months versus 40.7 months (HR 0.50).
“Consistent with the results reported previously, the median [time from random assignment to discontinuation of study treatment or death] TDT (data maturity 98.2%) was 24.6 months (95% CI, 24.0 to 24.8) in the olaparib group compared with 13.8 months (95% CI, 11.2 to 16.4) in the placebo group, with an HR of 0.63 (95% CI, 0.51 to 0.78).”
The study, published in the Journal of Clinical Oncology [link here], said the safety profile of maintenance olaparib was consistent with that previously reported.
The most common AEs of any grade reported in olaparib patients were nausea, fatigue/asthenia, vomiting, and anaemia, and the most serious AEs were anaemia and neutropenia.
“The incidence of myelodysplastic syndrome and acute myeloid leukaemia remained low, and new primary malignancies remained balanced between treatment groups.”
The investigators, including Dr Michael Friedlander from the Prince of Wales Hospital and University of NSW, said SOLO1 is the first study to indicate a clinically meaningful improvement in OS with PARP inhibitor maintenance therapy in the first-line setting.
“The results of SOLO1 emphasise the importance of both testing for both germline and somatic BRCA mutations and providing PARP inhibitor maintenance therapy to all BRCA-mutated patients with advanced disease in the first-line setting, rather than delaying the introduction of PARP inhibitors until patients have experienced relapse.”
“On the basis of the results of SOLO1, maintenance therapy with olaparib is capped at 2 years in the first-line setting although patients with evidence of disease at this time point can be treated beyond 2 years.”
The study was supported by AstraZeneca.