Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial
Mené dans 15 pays sur 391 patientes atteintes d'un cancer de l'ovaire de stade avancé récemment diagnostiqué et présentant une mutation BRCA, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'olaparib en traitement d'entretien après une réponse partielle ou complète à une chimiothérapie à base de sels de platine (durées médianes de suivi : 4,8 et 5 ans)
Résumé en anglais
Background : There is a high unmet need for treatment regimens that increase the chance of long-termremission and possibly cure for women with newly diagnosed advanced ovarian cancer.In the primary analysis of SOLO1/GOG 3004, the poly(ADP-ribose) polymerase (PARP)inhibitor olaparib significantly improved progression-free survival versus placebo in patients with a BRCA mutation; median progression-free survival was not reached. Here, we report an updated,post-hoc analysis of progression-free survival from SOLO1, after 5 years of follow-up.
Methods : SOLO1 was a randomised, double-blind, placebo-controlled, phase 3 trial, done across118 centres in 15 countries, that enrolled patients aged 18 years or older with anEastern Cooperative Oncology Group performance status of 0–1 and with BRCA-mutated, newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer with a complete or partial clinical response after platinum-based chemotherapy. Patientswere randomly assigned (2:1) via a web-based or interactive voice-response systemto receive olaparib (300 mg twice daily) or placebo tablets orally as maintenance monotherapy for up to 2 years; randomisation was by blocks and was stratified accordingto clinical response after platinum-based chemotherapy. Patients, treatment providers,and data assessors were masked to group assignment. The primary endpoint was investigator-assessed progression-free survival. Efficacy is reported in the intention-to-treat populationand safety in patients who received at least one dose of treatment. The data cutofffor this updated, post-hoc analysis was March 5, 2020. This trial is registered with ClinicalTrials.gov (NCT01844986) and is ongoing but closed to new participants.
Findings : Between Sept 3, 2013, and March 6, 2015, 260 patients were randomly assigned to olaparib and 131 to placebo. The median treatment duration was 24·6 months (IQR 11·2–24·9)in the olaparib group and 13·9 months (8·0–24·8) in the placebo group; median follow-up was 4·8 years (2·8–5·3) in the olaparib group and 5·0 years (2·6–5·3) in the placebogroup. In this post-hoc analysis, median progression-free survival was 56·0 months(95% CI 41·9–not reached) with olaparib versus 13·8 months (11·1–18·2) with placebo(hazard ratio 0·33 [95% CI 0·25–0·43]). The most common grade 3–4 adverse events wereanaemia (57 [22%] of 260 patients receiving olaparib vs two [2%] of 130 receiving placebo) and neutropenia (22 [8%] vs six [5%]), and serious adverse events occurred in 55 (21%) of 260 patients in theolaparib group and 17 (13%) of 130 in the placebo group. No treatment-related adverseevents that occurred during study treatment or up to 30 days after discontinuationwere reported as leading to death. No additional cases of myelodysplastic syndromeor acute myeloid leukaemia were reported since the primary data cutoff, includingafter the 30-day safety follow-up period.
Interpretation : For patients with newly diagnosed advanced ovarian cancer and a BRCA mutation, after, to our knowledge, the longest follow-up for any randomised controlledtrial of a PARP inhibitor in this setting, the benefit derived from 2 years' maintenance therapy with olaparib was sustained beyond the end of treatment, extending medianprogression-free survival past 4·5 years. These results support the use of maintenanceolaparib as a standard of care in this setting.
