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.
- MeSH
- analýza přežití MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- everolimus škodlivé účinky terapeutické užití MeSH
- gastrointestinální nádory farmakoterapie mortalita patologie psychologie MeSH
- hodnocení rizik MeSH
- internacionalita MeSH
- invazivní růst nádoru patologie MeSH
- kvalita života * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory plic farmakoterapie mortalita patologie psychologie MeSH
- neuroendokrinní nádory farmakoterapie mortalita patologie psychologie MeSH
- placeba terapeutické užití MeSH
- přežití po terapii bez příznaků nemoci MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- senioři MeSH
- staging nádorů MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Klíčová slova
- studie CheckMate -025,
- MeSH
- analýza přežití MeSH
- antitumorózní látky farmakologie terapeutické užití MeSH
- everolimus farmakologie terapeutické užití MeSH
- klinické zkoušky, fáze III jako téma MeSH
- kvalita života MeSH
- lidé MeSH
- monoklonální protilátky * farmakologie terapeutické užití MeSH
- nádory ledvin * farmakoterapie MeSH
- nivolumab MeSH
- protokoly protinádorové léčby MeSH
- průzkumy a dotazníky MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- adjuvantní chemoterapie MeSH
- inhibitory aromatasy škodlivé účinky terapeutické užití MeSH
- klinický obraz nemoci MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prsu * farmakoterapie MeSH
- návaly chemicky indukované epidemiologie MeSH
- nežádoucí účinky léčiv psychologie MeSH
- postmenopauzální osteoporóza chemicky indukované epidemiologie MeSH
- tamoxifen škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- MeSH
- anemie farmakoterapie MeSH
- erythropoetin terapeutické užití MeSH
- karcinom farmakoterapie MeSH
- kvalita života MeSH
- lidé MeSH
- placebo efekt MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH