The efficacy of olaparib as maintenance therapy in newly diagnosed advanced ovarian cancer with BRCA mutation: 5-year follow-up from SOLO-1 trial
Patients with newly diagnosed advanced ovarian cancer have a high risk of recurrence, with a 5-year survival rate of approximately 30% and 50%. Therefore, treatments for this scenario aim to delay the recurrence of the disease, extend prolonged survival and, for some patients, increase the chances of cure.
In SOLO1 (NCT01844986; GOG-3004), patients with ovarian cancer and BRCA gene mutation (BRCAm), who responded after first-line platinum-based chemotherapy, had a significant progression-free survival (PFS) benefit with maintenance olaparib versus placebo. After an average follow-up of 41 months, the risk of disease progression or death was 70% lower with olaparib than with placebo (Kaplan-Meier estimate of the disease-free progression-free survival rate at 3 years: 60% versus 27%; HR for disease progression or death: 0.30; p <0.001) .
SOLO1 is an international, phase III, double-blind, randomized trial to evaluate the efficacy of olaparib as maintenance therapy in patients with newly diagnosed high-grade endometrioid or serous ovarian cancer (figure III or IV), primary peritoneal cancer or fallopian tube cancer (or a combination thereof) with a mutation in BRCA1, BRCA2, or both (BRCA1 / 2) who had a complete or partial clinical response after platinum-based chemotherapy.
In total, 391 patients were randomised in a 2:1 ratio to receive olaparib 300 mg orally twice daily or placebo for up to two years or until disease progression. The ESMO 2020 Virtual Congress presented data from 5 years of follow – up, with analysis of the information carried out until the date of March 5, 2020.
The researcher evaluated PFS and recurrence-free survival (RFS) using the modified RECIST1.1. For patients in complete response (Cr) at baseline, SLR was defined post hoc as the time from randomisation to disease recurrence (new imaging lesions) or death.
In total, 260 patients were randomly assigned to olaparib and 131 to the placebo group (mean duration of treatment 24.6 versus 13.9 months, respectively). After a median of 4.8 and 5.0 years of follow-up, the median PFS was 56 versus 13.8 months. Among patients with a complete response at baseline, the risk of disease recurrence or death was reduced by 63%.
The safety profile of olaparib was consistent with the above observations. No new cases of myelodysplastic syndrome or acute myeloid leukaemia have been reported and the incidence of new primary malignancies has been balanced between the arms (olaparib, 7/260 [3%]; placebo, 5/130 [4%]).
The authors concluded that for patients with BRCAm and newly diagnosed advanced ovarian cancer, the benefit of 2 years of maintenance with olaparib was maintained beyond the end of treatment, and after 5 years, almost half of the patients were progression-free versus 20% in the placebo group. More than 50% of patients with complete response after first-line platinum-based chemotherapy remained relapse-free after 5 years. The 5-year follow-up data is the longest of any PARP inhibitor in this setting.
Moore K, Colombo N, Exchange G, Kim BG, Oaknin A, Friedlander m, Lisyanskaya A, Floquet a, Leary a, Sonke GS, Gourley C. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. New England Journal of Medicine. 2018 Dec 27; 379(26): 2495-505.
Presentation number 811mo-Banerjee, S. Maintenance olaparib for patients (pts) with newly diagnosed, advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): 5-year (y) follow-up (f/u) from SOLO1. ESMO 2020.
DiSilvestro, P et al. Efficacy of maintenance Olaparib for Patients with Newly Diagnosed advanced Ovarian Cancer With a BRCA Mutation: Subgroup analysis Findings From the SOLO1 Trial. Journal of Clinical Oncology-published online before print August 4, 2020