Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial
Mené dans 16 pays sur 295 patientes atteintes d'un cancer de l'ovaire récidivant et sensible aux sels de platine et présentant une mutation BRCA, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité de l'olaparib dispensé sous forme de comprimés en traitement d'entretien (durée médiane de suivi : 65,7 mois)
Background : Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has previously been shownto extend progression-free survival versus placebo when given to patients with relapsedhigh-grade serous or endometrioid ovarian cancer who were platinum sensitive and whohad a BRCA1 or BRCA2 (BRCA1/2) mutation, as part of the SOLO2/ENGOT-Ov21 trial. The aim of this final analysisis to investigate the effect of olaparib on overall survival. Methods : This double-blind, randomised, placebo-controlled, phase 3 trial was done across 123 medical centres in 16 countries. Eligible patients were aged 18 years or older, hadan Eastern Cooperative Oncology Group performance status at baseline of 0–1, had histologicallyconfirmed, relapsed, high-grade serous or high-grade endometrioid ovarian cancer,including primary peritoneal or fallopian tube cancer, and had received two or moreprevious platinum regimens. Patients were randomly assigned (2:1) to receive olaparibtablets (300 mg in two 150 mg tablets twice daily) or matching placebo tablets usingan interactive web or voice-response system. Stratification was by response to previouschemotherapy and length of platinum-free interval. Treatment assignment was maskedto patients, treatment providers, and data assessors. The primary endpoint of progression-frees urvival has been reported previously. Overall survival was a key secondary endpointand was analysed in all patients as randomly allocated. Safety was assessed in allpatients who received at least one treatment dose. This trial is registered with ClinicalTrials.gov, NCT01874353, and is no longer recruiting patients. Findings : Between Sept 3, 2013 and Nov 21, 2014, 295 patients were enrolled. Patients were randomlyassigned to receive either olaparib (n=196 [66%]) or placebo (n=99 [34%]). One patient,randomised in error, did not receive olaparib. Median follow-up was 65·7 months (IQR63·6–69·3) with olaparib and 64·5 months (63·4–68·7) with placebo. Median overallsurvival was 51·7 months (95% CI 41·5–59·1) with olaparib and 38·8 months (31·4–48·6)with placebo (hazard ratio 0·74 [95% CI 0·54–1·00]; p=0·054), unadjusted for the 38%of patients in the placebo group who received subsequent PARP inhibitor therapy. Themost common grade 3 or worse treatment-emergent adverse event was anaemia (which occurredin 41 [21%] of 195 patients in the olaparib group and two [2%] of 99 patients in theplacebo group). Serious treatment-emergent adverse events were reported in 50 (26%)of 195 patients receiving olaparib and eight (8%) of 99 patients receiving placebo.Treatment-emergent adverse events with a fatal outcome occurred in eight (4%) of the195 patients receiving olaparib, six of which were judged to be treatment-related(attributed to myelodysplastic syndrome [n=3] and acute myeloid leukaemia [n=3]). Interpretation : Olaparib provided a median overall survival benefit of 12·9 months compared with placeboin patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Although statistical significance was not reached, these findings are arguablyclinically meaningful and support the use of maintenance olaparib in these patients.
The Lancet Oncology 2021