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.

Background: In the phase 3 SOLO1 trial, maintenance olaparib provided a significant progression-free survival 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 15 countries. Eligible patients were aged 18 years or older; had an Eastern Cooperative Oncology Group performance status score of 0-1; had newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer 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 placebo twice per day using an interactive voice and web response system and were treated for 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 endpoint was the change from baseline in the Functional Assessment of Cancer Therapy-Ovarian Cancer Trial Outcome Index (TOI) score for the first 24 months. TOI scores range from 0 to 100 (higher scores indicated better HRQOL), with a clinically meaningful difference defined as a difference of at least 10 points. Prespecified exploratory endpoints were quality-adjusted progression-free survival and time without significant symptoms of 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 study treatment), with a median duration of follow-up of 40·7 months (IQR 34·9-42·9) for olaparib and 41·2 months (32·2-41·6) for placebo. There was no clinically meaningful change 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 olaparib in the newly diagnosed setting was achieved with no detrimental effect on patients' HRQOL and was supported by clinically meaningful quality-adjusted progression-free survival and TWiST benefits with maintenance olaparib versus placebo.
Funding: AstraZeneca and Merck Sharp & Dohme.
Competing Interests: Declaration of interests MF reports institutional research support, personal fees, consulting fees, and travel support from AstraZeneca; institutional research support and personal fees from Novartis; institutional research support from Beigene; personal fees from Takeda, GlaxoSmithKline, Lilly and Merck Sharp & Dohme, and being on a trial management committee for AbbVie, outside the submitted work. KNM reports personal fees from AstraZeneca, AbbVie, Aravive, Eisai, GlaxoSmithKline, Tesaro, Genentech/Roche, Immunogen, Merck, Myriad, Mersana, VBL Therapeutics, Vavotar, and Tarveda, outside the submitted work. NC reports personal fees from AstraZeneca during the conduct of the study; and personal fees from Merck Sharp & Dohme, Roche, Tesaro, GlaxoSmithKline, Clovis Oncology, PharmaMar, Pfizer, Amgen, Novartis, Biocad, and Immunogen, outside the submitted work. AOa reports personal fees, travel and accommodation support, and grants from PharmaMar and Clovis Oncology; personal fees, and travel and accomodation support from Roche and AstraZeneca; personal fees and grants from Tesaro and Immunogen; personal fees from Genmab; and grants from AbbVie Deutchland, Ability Pharmaceuticals, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics, Eisai, F Hoffmann-La Roche, Regeneron, Merck Sharp & Dohme de España, Millennium Pharmaceuticals, and Bristol Myers Squibb, outside the submitted work. GSS reports institutional reimbursement for patient accrual and medical writing assistance from AstraZeneca, during the conduct of the study; and institutional research support from Merck, Novartis, and Roche, outside the submitted work. CG reports grants from AstraZeneca during the conduct of the study; grants and personal fees from AstraZeneca, Clovis Oncology, GlaxoSmithKline, Tesaro, Nucana, and Sierra Oncology; grants from Aprea and Novartis; personal fees from Roche, Foundation One, Chugai, Merck Sharp & Dohme, and Cor2Ed, outside the submitted work; and patents for molecular diagnostic tests for cancer. SB reports grants and personal fees from AstraZeneca and Tesaro; personal fees from Clovis Oncology, GlaxoSmithKline, Merck Sharp & Dohme, Pfizer, Mersana, Merck Serono, Roche, Seattle Genetics, Genmab, Amgen, and Immunogen; and travel support from Nucana, outside the submitted work. AOz reports being a principal investigator of investigator-initiated studies with AstraZeneca, that his institution has received grant funding from AstraZeneca, and being a steering committee member (non-compensated) for AstraZeneca, Clovis Oncology, and GlaxoSmithKline. AG-M reports personal fees from Amgen, AstraZeneca, Clovis Oncology, Genmab, Immunogen, Merck Sharp & Dohme, Novartis, Oncoinvent, Pfizer/Merck, PharmaMar, Roche, and Sotio; and grants and personal fees from GlaxoSmithKline, and Tesaro, outside the submitted work. CA reports personal fees from AstraZeneca/Merck, Tesaro, Immunogen, Eisai/Merck, Mersana Therapeutics, and Roche/Genentech; grants from Genentech; and grants and personal fees from AstraZeneca, Clovis Oncology, and AbbVie, outside the submitted work. JL reports personal fees from AstraZeneca, Clovis Oncology, Genentech, Regeneron, Tesaro, and GlaxoSmithKline; and advisory board fees from Merck, outside the submitted work; and funding to her institution as principal investigator on trials from 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, CytomX Therapeutics, GlaxoSmithKline, Regeneron, Surface Oncology, Tesaro, and Vigeo Therapeutics. CM reports grants from Syros, Deciphera, AstraZeneca, Astellas Pharma, Tesaro, GlaxoSmithKline, Seattle Genetics, Regeneron, and Moderna, outside the submitted work. FS reports personal fees and non-financial support from Roche, AstraZeneca, Tesaro, Merck Sharp & Dohme, and PharmaMar; and personal fees from GlaxoSmithKline and Clovis Oncology, outside the submitted work. ESL, RH, and EF report full-time employment with AstraZeneca during the conduct of the study and AstraZeneca stock ownership. EP reports employment with Parexel, which has received consultancy fees from AstraZeneca, during the conduct of the study. PDS reports personal fees from AstraZeneca, GlaxoSmithKline, Tesaro, and AbbVie, outside the submitted work. All other authors declare no competing interests.
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