PMID- 30026002 OWN - NLM STAT- MEDLINE DCOM- 20190424 LR - 20210210 IS - 1474-5488 (Electronic) IS - 1470-2045 (Print) IS - 1470-2045 (Linking) VI - 19 IP - 8 DP - 2018 Aug TI - 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. PG - 1126-1134 LID - S1470-2045(18)30343-7 [pii] LID - 10.1016/S1470-2045(18)30343-7 [doi] AB - 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. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Friedlander, Michael AU - Friedlander M AD - University of New South Wales Clinical School, Prince of Wales Hospital, Randwick, NSW, Australia. Electronic address: m.friedlander@unsw.edu.au. FAU - Gebski, Val AU - Gebski V AD - NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia. FAU - Gibbs, Emma AU - Gibbs E AD - NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia. FAU - Davies, Lucy AU - Davies L AD - NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia; Nuffield Department of Population Health, University of Oxford, Oxford, UK. FAU - Bloomfield, Ralph AU - Bloomfield R AD - AstraZeneca, Cambridge, UK. FAU - Hilpert, Felix AU - Hilpert F AD - Jerusalem Hospital, Hamburg, Germany. FAU - Wenzel, Lari B AU - Wenzel LB AD - University of California, Irvine, CA, USA. FAU - Eek, Daniel AU - Eek D AD - AstraZeneca, Gothenburg, Sweden. FAU - Rodrigues, Manuel AU - Rodrigues M AD - Institut Curie, Paris, France. FAU - Clamp, Andrew AU - Clamp A AD - The Christie and University of Manchester, Manchester, UK. FAU - Penson, Richard T AU - Penson RT AD - Harvard Medical School, Boston, MA, USA. FAU - Provencher, Diane AU - Provencher D AD - University of Montreal, Montreal, QC, Canada. FAU - Korach, Jacob AU - Korach J AD - Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel. FAU - Huzarski, Tomasz AU - Huzarski T AD - Pomeranian Medical University, Szczecin, Poland. FAU - Vidal, Laura AU - Vidal L AD - Hospital Clinic, Barcelona, Spain. FAU - Salutari, Vanda AU - Salutari V AD - Policlinico Universitario Agostino Gemelli, Rome, Italy. FAU - Scott, Clare AU - Scott C AD - The Walter and Eliza Hall Institute of Medical Research, Parkville, VA, Australia. FAU - Nicoletto, Maria Ornella AU - Nicoletto MO AD - Istituto Oncologico Veneto, Padova, Italy. FAU - Tamura, Kenji AU - Tamura K AD - National Cancer Center Hospital, Tokyo, Japan. FAU - Espinoza, David AU - Espinoza D AD - NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia. FAU - Joly, Florence AU - Joly F AD - Centre Francois Baclesse, Caen, France. FAU - Pujade-Lauraine, Eric AU - Pujade-Lauraine E AD - Universite Paris Descartes, AP-HP, Paris, France. LA - eng SI - ClinicalTrials.gov/NCT01874353 GR - P30 CA062203/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20180717 PL - England TA - Lancet Oncol JT - The Lancet. Oncology JID - 100957246 RN - 0 (Antineoplastic Agents) RN - 0 (BRCA1 Protein) RN - 0 (BRCA1 protein, human) RN - 0 (BRCA2 Protein) RN - 0 (BRCA2 protein, human) RN - 0 (Phthalazines) RN - 0 (Piperazines) RN - WOH1JD9AR8 (olaparib) SB - IM CIN - Lancet Oncol. 2018 Oct;19(10):e504. PMID: 30303117 MH - Adult MH - Aged MH - Antineoplastic Agents/*therapeutic use MH - BRCA1 Protein/genetics MH - BRCA2 Protein/genetics MH - Carcinoma, Ovarian Epithelial/*drug therapy/genetics/mortality MH - Female MH - Humans MH - Maintenance Chemotherapy/methods MH - Middle Aged MH - Mutation MH - Neoplasm Recurrence, Local/*drug therapy MH - Phthalazines/*therapeutic use MH - Piperazines/*therapeutic use MH - Progression-Free Survival MH - *Quality of Life MH - Surveys and Questionnaires PMC - PMC7869962 MID - NIHMS1656321 EDAT- 2018/07/22 06:00 MHDA- 2019/04/25 06:00 PMCR- 2021/02/08 CRDT- 2018/07/21 06:00 PHST- 2018/03/14 00:00 [received] PHST- 2018/04/26 00:00 [revised] PHST- 2018/04/26 00:00 [accepted] PHST- 2018/07/22 06:00 [pubmed] PHST- 2019/04/25 06:00 [medline] PHST- 2018/07/21 06:00 [entrez] PHST- 2021/02/08 00:00 [pmc-release] AID - S1470-2045(18)30343-7 [pii] AID - 10.1016/S1470-2045(18)30343-7 [doi] PST - ppublish SO - Lancet Oncol. 2018 Aug;19(8):1126-1134. doi: 10.1016/S1470-2045(18)30343-7. Epub 2018 Jul 17.