Patient-centred outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance olaparib or placebo (SOLO1): a randomised, 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 du taux de réponse, et l'intérêt, du point de vue de la qualité de vie, d'un traitement d'entretien à base d'olaparib, après une réponse à une chimiothérapie à base de sels de platine (durée médiane de suivi : 40,7 mois)
Background : In the phase 3 SOLO1 trial, maintenance olaparib provided a significant progression-freesurvival benefit versus placebo in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation in response after platinum-based chemotherapy. We analysed health-related quality of life (HRQOL) and patient-centred outcomes in SOLO1, and the effect of radiological disease progression on health status. Methods : SOLO1 is a randomised, double-blind, international trial done in 118 centres and 15countries. Eligible patients were aged 18 years or older; had an Eastern CooperativeOncology Group performance status score of 0–1; had newly diagnosed, advanced, high-gradeserous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tubecancer with a BRCA mutation; and were in clinical complete or partial response to platinum-based chemotherapy.Patients were randomly assigned (2:1) to either 300 mg olaparib tablets or placebotwice per day using an interactive voice and web response system and were treatedfor up to 2 years. Treatment assignment was masked for patients and for clinicians giving the interventions, and those collecting and analysing the data. Randomisation was stratified by response to platinum-based chemotherapy (clinical complete or partial response). HRQOL was a secondary endpoint and the prespecified primary HRQOL endpointwas the change from baseline in the Functional Assessment of Cancer Therapy–OvarianCancer Trial Outcome Index (TOI) score for the first 24 months. TOI scores range from0 to 100 (higher scores indicated better HRQOL), with a clinically meaningful differencedefined as a difference of at least 10 points. Prespecified exploratory endpointswere quality-adjusted progression-free survival and time without significant symptomsof toxicity (TWiST). HRQOL endpoints were analysed in all randomly assigned patients.The trial is ongoing but closed to new participants. This trial is registered with ClinicalTrials.gov, NCT01844986. Findings : Between Sept 3, 2013, and March 6, 2015, 1084 patients were enrolled. 693 patients were ineligible, leaving 391 eligible patients who were randomly assigned to olaparib(n=260) or placebo (n=131; one placebo patient withdrew before receiving any studytreatment), with a median duration of follow-up of 40·7 months (IQR 34·9–42·9) forolaparib and 41·2 months (32·2–41·6) for placebo. There was no clinically meaningfulchange in TOI score at 24 months within or between the olaparib and placebo groups(adjusted mean change in score from baseline over 24 months was 0·30 points [95% CI −0·72 to 1·32] in the olaparib group vs 3·30 points [1·84 to 4·76] in the placebo group; between-group difference of −3·00,95% CI −4·78 to −1·22; p=0·0010). Mean quality-adjusted progression-free survival(olaparib 29·75 months [95% CI 28·20–31·63] vs placebo 17·58 [15·05–20·18]; difference 12·17 months [95% CI 9·07–15·11], p<0·0001)and the mean duration of TWiST (olaparib 33·15 months [95% CI 30·82–35·49] vs placebo 20·24 months [17·36–23·11]; difference 12·92 months [95% CI 9·30–16·54];p<0·0001) were significantly longer with olaparib than with placebo. Interpretation : The substantial progression-free survival benefit provided by maintenance olaparibin the newly diagnosed setting was achieved with no detrimental effect on patients'HRQOL and was supported by clinically meaningful quality-adjusted progression-freesurvival and TWiST benefits with maintenance olaparib versus placebo.
The Lancet Oncology 2021