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

J 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

PAVEL, M.E., S. SINGH, J.R. STROSBERG, L. BUBUTEISHVILI-PACAUD, E. DEGTYAREV et. al.

Basic information

Original name

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

Authors

PAVEL, M.E. (276 Germany), S. SINGH (124 Canada), J.R. STROSBERG (840 United States of America), L. BUBUTEISHVILI-PACAUD (756 Switzerland), E. DEGTYAREV (756 Switzerland), M.P. NEARY (840 United States of America), C. CARNAGHI (380 Italy), Jiří TOMÁŠEK (203 Czech Republic, guarantor, belonging to the institution), E. WOLIN (840 United States of America), M. RADERER (40 Austria), H. LAHNER (276 Germany), J.W. VALLE (826 United Kingdom of Great Britain and Northern Ireland), R. POMMIER (840 United States of America), E. VAN CUTSEM (56 Belgium), M.E.T. TESSELAAR (528 Netherlands), G. DELLE FAVE (380 Italy), R. BUZZONI (380 Italy), M. HUNGER (276 Germany), J. ERIKSSON (752 Sweden), D. CELLA (840 United States of America), J.F. RICCI (756 Switzerland), N. FAZIO (380 Italy), M.H. KULKE (840 United States of America) and J.C. YAO (840 United States of America)

Edition

Lancet Oncology, New York, Elsevier Science INC, 2017, 1470-2045

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 36.421

RIV identification code

RIV/00216224:14110/17:00099925

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/S1470-2045(17)30471-0

UT WoS

000411843500056

Keywords in English

RADIANT-4; everolimus versus placebo

Abstract

V originále

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.

Citovat

PAVEL, M.E., S. SINGH, J.R. STROSBERG, L. BUBUTEISHVILI-PACAUD, E. DEGTYAREV, M.P. NEARY, C. CARNAGHI, Jiří TOMÁŠEK, E. WOLIN, M. RADERER, H. LAHNER, J.W. VALLE, R. POMMIER, E. VAN CUTSEM, M.E.T. TESSELAAR, G. DELLE FAVE, R. BUZZONI, M. HUNGER, J. ERIKSSON, D. CELLA, J.F. RICCI, N. FAZIO, M.H. KULKE and J.C. YAO. 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. New York: Elsevier Science INC, 2017, vol. 18, No 10, p. 1411-1422. ISSN 1470-2045. Available from: https://dx.doi.org/10.1016/S1470-2045(17)30471-0.

@article{1407094,
   author = {Pavel, M.E. and Singh, S. and Strosberg, J.R. and BubuteishviliandPacaud, L. and Degtyarev, E. and Neary, M.P. and Carnaghi, C. and Tomášek, Jiří and Wolin, E. and Raderer, M. and Lahner, H. and Valle, J.W. and Pommier, R. and Van Cutsem, E. and Tesselaar, M.E.T. and Delle Fave, G. and Buzzoni, R. and Hunger, M. and Eriksson, J. and Cella, D. and Ricci, J.F. and Fazio, N. and Kulke, M.H. and Yao, J.C.},
   article_location = {New York},
   article_number = {10},
   doi = {http://dx.doi.org/10.1016/S1470-2045(17)30471-0},
   keywords = {RADIANT-4; everolimus versus placebo},
   language = {eng},
   issn = {1470-2045},
   journal = {Lancet Oncology},
   title = {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},
   volume = {18},
   year = {2017}
}

TY  - JOUR
ID  - 1407094
AU  - Pavel, M.E. - Singh, S. - Strosberg, J.R. - Bubuteishvili-Pacaud, L. - Degtyarev, E. - Neary, M.P. - Carnaghi, C. - Tomášek, Jiří - Wolin, E. - Raderer, M. - Lahner, H. - Valle, J.W. - Pommier, R. - Van Cutsem, E. - Tesselaar, M.E.T. - Delle Fave, G. - Buzzoni, R. - Hunger, M. - Eriksson, J. - Cella, D. - Ricci, J.F. - Fazio, N. - Kulke, M.H. - Yao, J.C.
PY  - 2017
TI  - 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
JF  - Lancet Oncology
VL  - 18
IS  - 10
SP  - 1411-1422
EP  - 1411-1422
PB  - Elsevier Science INC
SN  - 14702045
KW  - RADIANT-4
KW  - everolimus versus placebo
N2  - 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.
ER  -

PAVEL, M.E., S. SINGH, J.R. STROSBERG, L. BUBUTEISHVILI-PACAUD, E. DEGTYAREV, M.P. NEARY, C. CARNAGHI, Jiří TOMÁŠEK, E. WOLIN, M. RADERER, H. LAHNER, J.W. VALLE, R. POMMIER, E. VAN CUTSEM, M.E.T. TESSELAAR, G. DELLE FAVE, R. BUZZONI, M. HUNGER, J. ERIKSSON, D. CELLA, J.F. RICCI, N. FAZIO, M.H. KULKE and J.C. YAO. 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. \textit{Lancet Oncology}. New York: Elsevier Science INC, 2017, vol.~18, No~10, p.~1411-1422. ISSN~1470-2045. Available from: https://dx.doi.org/10.1016/S1470-2045(17)30471-0.

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