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Health-related quality of life for everolimus versus placebo in patients with advanced, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (RADIANT-4): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
ME. Pavel, S. Singh, JR. Strosberg, L. Bubuteishvili-Pacaud, E. Degtyarev, MP. Neary, C. Carnaghi, J. Tomasek, E. Wolin, M. Raderer, H. Lahner, JW. Valle, R. Pommier, E. Van Cutsem, MET. Tesselaar, GD. Fave, R. Buzzoni, M. Hunger, J. Eriksson, D....
Language English Country Great Britain
Document type Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial
NLK
ProQuest Central
from 2000-09-01 to 2 months ago
Nursing & Allied Health Database (ProQuest)
from 2000-09-01 to 2 months ago
Health & Medicine (ProQuest)
from 2000-09-01 to 2 months ago
Public Health Database (ProQuest)
from 2000-09-01 to 2 months ago
- MeSH
- Survival Analysis MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Everolimus adverse effects therapeutic use MeSH
- Gastrointestinal Neoplasms drug therapy mortality pathology psychology MeSH
- Risk Assessment MeSH
- Internationality MeSH
- Neoplasm Invasiveness pathology MeSH
- Quality of Life * MeSH
- Middle Aged MeSH
- Humans MeSH
- Lung Neoplasms drug therapy mortality pathology psychology MeSH
- Neuroendocrine Tumors drug therapy mortality pathology psychology MeSH
- Placebos therapeutic use MeSH
- Disease-Free Survival MeSH
- Prognosis MeSH
- Proportional Hazards Models MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: In the phase 3 RADIANT-4 trial, everolimus increased progression-free survival compared with placebo in patients with advanced, progressive, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (NETs). We now report the health-related quality of life (HRQOL) secondary endpoint. METHODS: RADIANT-4 is a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial done in 97 centres in 25 countries worldwide. Adults (aged ≥18 years) were eligible for the study if they had pathologically confirmed, advanced (unresectable or metastatic), non-functional, well-differentiated (grade 1 or 2) NETs of lung or gastrointestinal origin. Patients were randomly allocated (2:1) using block randomisation (block size of three) by an interactive voice response system to receive oral everolimus (10 mg per day) or placebo, both with best supportive care, with stratification by tumour origin, WHO performance status, and previous somatostatin analogue treatment. HRQOL was assessed with the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at baseline (visit 2, day 1), every 8 weeks (± 1 week) during the study for the first 12 months after randomisation, and every 12 weeks thereafter until study drug discontinuation. The primary endpoint, reported previously, was progression-free survival assessed by central review; HRQOL was a prespecified secondary endpoint. The prespecified secondary outcome measure was time to definitive deterioration (≥7 points) in FACT-G total score. Analyses were done on the full analysis set, consisting of all randomised patients, by intention to treat. Only data obtained while receiving the randomly allocated treatment were included in this analysis. Enrolment for RADIANT-4 was completed on Aug 23, 2013, but the trial is ongoing pending final analysis of the key secondary endpoint of overall survival. This trial is registered with ClinicalTrials.gov, number NCT01524783. FINDINGS: Between April 3, 2012, and Aug 23, 2013, 302 patients were enrolled; 205 were randomly allocated everolimus and 97 were assigned placebo. At baseline, 193 (94%) of 205 patients assigned everolimus and 95 (98%) of 97 allocated placebo had completed either fully or partly the FACT-G questionnaire; at week 48, 70 (83%) of 84 patients assigned everolimus and 22 (85%) of 26 allocated placebo completed FACT-G. Median time to definitive deterioration in FACT-G total score was 11·27 months (95% CI 9·27-19·35) with everolimus and 9·23 months (5·52-not estimable) with placebo (adjusted hazard ratio 0·81, 95% CI 0·55-1·21; log-rank p=0·31). INTERPRETATION: HRQOL was maintained for patients with advanced, non-functional, gastrointestinal or lung NETs, with no relevant differences noted between the everolimus and placebo groups. In view of the previous RADIANT-4 findings of longer progression-free survival with everolimus, our findings suggest that everolimus delays disease progression while preserving overall HRQOL, even with the usual toxic effects related to active targeted drug treatment for cancer. FUNDING: Novartis Pharmaceuticals.
Department of Gastrointestinal Oncology Moffitt Cancer Center Tampa FL USA
Department of Internal Medicine 1 Division of Oncology Klinik f Innere Medizin 1 AKH Vienna Austria
Department of Medical Oncology Antoni van Leeuwenhoek Amsterdam Netherlands
Department of Medical Oncology Montefiore Einstein Center for Cancer Care Bronx NY USA
Department of Medical Oncology The Christie NHS Foundation Trust Manchester UK
Department of Medical Social Sciences Northwestern University Chicago IL USA
Department of Medicine 1 Division of Endocrinology Universitätsklinikum Erlangen Erlangen Germany
Division of Medical Oncology and Hematology Sunnybrook Health Sciences Centre Toronto ON Canada
Division of Surgical Oncology Oregon Health and Science University Portland OR USA
Medical Oncology and Solid Tumor Oncology Dana Farber Cancer Institute Boston MA USA
Novartis Pharma AG Basel Switzerland
Novartis Pharmaceuticals Corporation East Hanover NJ USA
Oncology Unit Humanitas Clinical and Research Centre Rozzano Italy
University Hospitals Leuven and KU Leuven Digestive Oncology Leuven Belgium
References provided by Crossref.org
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- $a Pavel, Marianne E $u Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany; Department of Medicine 1, Division of Endocrinology, Universitätsklinikum Erlangen, Erlangen, Germany.
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