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Health-related quality of life and patient-centred outcomes with olaparib maintenance after chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT Ov-21): a placebo-controlled, phase 3 randomised trial.
Friedlander, Michael; Gebski, Val; Gibbs, Emma; Davies, Lucy; Bloomfield, Ralph; Hilpert, Felix; Wenzel, Lari B; Eek, Daniel; Rodrigues, Manuel; Clamp, Andrew; Penson, Richard T; Provencher, Diane; Korach, Jacob; Huzarski, Tomasz; Vidal, Laura; Salutari, Vanda; Scott, Clare; Nicoletto, Maria Ornella; Tamura, Kenji; Espinoza, David; Joly, Florence; Pujade-Lauraine, Eric.
Afiliação
  • Friedlander M; University of New South Wales Clinical School, Prince of Wales Hospital, Randwick, NSW, Australia. Electronic address: m.friedlander@unsw.edu.au.
  • Gebski V; NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia.
  • Gibbs E; NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia.
  • Davies L; NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia; Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Bloomfield R; AstraZeneca, Cambridge, UK.
  • Hilpert F; Jerusalem Hospital, Hamburg, Germany.
  • Wenzel LB; University of California, Irvine, CA, USA.
  • Eek D; AstraZeneca, Gothenburg, Sweden.
  • Rodrigues M; Institut Curie, Paris, France.
  • Clamp A; The Christie and University of Manchester, Manchester, UK.
  • Penson RT; Harvard Medical School, Boston, MA, USA.
  • Provencher D; University of Montreal, Montreal, QC, Canada.
  • Korach J; Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel.
  • Huzarski T; Pomeranian Medical University, Szczecin, Poland.
  • Vidal L; Hospital Clinic, Barcelona, Spain.
  • Salutari V; Policlinico Universitario Agostino Gemelli, Rome, Italy.
  • Scott C; The Walter and Eliza Hall Institute of Medical Research, Parkville, VA, Australia.
  • Nicoletto MO; Istituto Oncologico Veneto, Padova, Italy.
  • Tamura K; National Cancer Center Hospital, Tokyo, Japan.
  • Espinoza D; NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia.
  • Joly F; Centre François Baclesse, Caen, France.
  • Pujade-Lauraine E; Université Paris Descartes, AP-HP, Paris, France.
Lancet Oncol ; 19(8): 1126-1134, 2018 08.
Article em En | MEDLINE | ID: mdl-30026002
ABSTRACT

BACKGROUND:

In the phase 3 SOLO2 trial (ENGOT Ov-21), maintenance therapy with olaparib tablets significantly prolonged progression-free survival (primary endpoint) compared with placebo in patients with a germline BRCA1 or BRCA2 (BRCA1/2) mutation and platinum-sensitive, relapsed ovarian cancer who had received two or more lines of previous chemotherapy. The most common subjective adverse effects included fatigue, nausea, and vomiting, which were typically low grade and self-limiting. Our a-priori hypothesis was that maintenance olaparib would not negatively affect health-related quality of life (HRQOL) and additionally that the prolongation of progression-free survival with olaparib would be underpinned by additional patient-centred benefits.

METHODS:

In SOLO2, 196 patients were randomly assigned to olaparib tablets (300 mg twice daily) and 99 to placebo. Randomisation was stratified by response to previous chemotherapy (complete vs partial) and length of platinum-free interval (>6-12 vs >12 months). The prespecified primary HRQOL analysis evaluated the change from baseline in the Trial Outcome Index (TOI) score during the first 12 months of the study. To be assessable, patients had to have an evaluable score at baseline and at least one evaluable follow-up form. Secondary planned quality-of-life (QOL) analyses included the duration of good quality of life (defined as time without significant symptoms of toxicity [TWiST] and quality-adjusted progression-free survival [QAPFS]). Efficacy and QOL outcomes were analysed in all randomly assigned patients (the full analysis set), and safety outcomes were analysed in all randomly assigned patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01874353, and is closed to new participants.

FINDINGS:

The adjusted average mean change from baseline over the first 12 months in TOI was -2·90 (95% CI -4·13 to -1·67) with olaparib and -2·87 (-4·64 to -1·10) with placebo (estimated difference -0·03; 95% CI -2·19 to 2·13; p=0·98). Mean QAPFS (13·96 [SD 10·96] vs 7·28 [5·22] months; difference 6·68, 95% CI 4·98-8·54) and mean duration of TWiST (15·03 [SD 12·79] vs 7·70 [6·42] months; difference 7·33, 95% CI 4·70-8·96) were significantly longer with olaparib than with placebo.

INTERPRETATION:

Olaparib maintenance therapy did not have a significant detrimental effect on HRQOL compared with placebo. There were clinically meaningful patient-centred benefits in both TWiST and QAPFS despite the adverse effects associated with olaparib. These patient-centred endpoints support the improvement in progression-free survival, the primary endpoint in SOLO2, and should be included in future trials of maintenance therapies.

FUNDING:

AstraZeneca.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ftalazinas / Piperazinas / Qualidade de Vida / Carcinoma Epitelial do Ovário / Recidiva Local de Neoplasia / Antineoplásicos Tipo de estudo: Clinical_trials / Diagnostic_studies Limite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Lancet Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ftalazinas / Piperazinas / Qualidade de Vida / Carcinoma Epitelial do Ovário / Recidiva Local de Neoplasia / Antineoplásicos Tipo de estudo: Clinical_trials / Diagnostic_studies Limite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Lancet Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2018 Tipo de documento: Article