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

Pavel ME, Singh S, Strosberg JR, Bubuteishvili-Pacaud L, Degtyarev E, Neary MP, Carnaghi C, Tomasek J, Wolin E, Raderer M, Lahner H, Valle JW, Pommier R, Van Cutsem E, Tesselaar MET, Delle Fave G, Buzzoni R, Hunger M, Eriksson J, Cella D, Ricci JF, Fazio N, Kulke MH, Yao JC (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 18

Pages Range: 1411-1422

Journal Issue: 10

DOI: 10.1016/S1470-2045(17)30471-0

Abstract

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.

Authors with CRIS profile

Involved external institutions

Sunnybrook Health Sciences Centre Canada (CA) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) University of Texas MD Anderson Cancer Center United States (USA) (US) Antoni van Leeuwenhoek Netherlands (NL) Wellmera AG Switzerland (CH) University of Manchester United Kingdom (GB) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Mapi Group Sweden (SE) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) Novartis AG Switzerland (CH) Vienna General Hospital / Allgemeines Krankenhaus der Stadt Wien (AKH) Austria (AT) Oregon Health and Science University (OSHU) United States (USA) (US) Universitätsklinikum Essen Germany (DE) Montefiore Medical Center United States (USA) (US) Dana–Farber Cancer Institute United States (USA) (US) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) Istituto Clinico Humanitas Italy (IT) Università degli studi "La Sapienza" Italy (IT) Masaryk University Czech Republic (CZ) Northwestern University United States (USA) (US)

How to cite

APA:

Pavel, M.E., Singh, S., Strosberg, J.R., Bubuteishvili-Pacaud, L., Degtyarev, E., Neary, M.P.,... Yao, J.C. (2017). 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. Lancet Oncology, 18(10), 1411-1422. https://dx.doi.org/10.1016/S1470-2045(17)30471-0

MLA:

Pavel, Marianne Ellen, et al. "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." Lancet Oncology 18.10 (2017): 1411-1422.

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