Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1): A phase III, international, randomized, placebo-controlled study

E. Van Cutsem, T. Yoshino, H. J. Lenz, S. Lonardi, A. Falcone, M. L. Limón, M. Saunders, A. Sobrero, Y. S. Park, R. Ferreiro, Y. S. Hong, J. Tomasek, H. Taniguchi, F. Ciardiello, J. Stoehr, Z. Oum'hamed, S. Vlassak, M. Studeny, G. Argiles

Research output: Contribution to journalArticle

Abstract

Background Angiogenesis is critical to colorectal cancer (CRC) growth and metastasis. Phase I/II studies have demonstrated the efficacy of nintedanib, a triple angiokinase inhibitor, in patients with metastatic CRC. This global, randomized, phase III study investigated the efficacy and safety of nintedanib in patients with refractory CRC after failure of standard therapies. Patients and methods Eligible patients (Eastern Cooperative Oncology Group performance status 0-1, with histologically/cytologically confirmed metastatic/locally advanced CRC adenocarcinoma unamenable to surgery and/or radiotherapy) were randomized 1: 1 to receive nintedanib (200 mg twice daily) or placebo (twice daily), until disease progression or undue toxicity. Patients were stratified by previous regorafenib, time from onset of metastatic disease to randomization, and region. Co-primary end points were overall survival (OS) and progression-free survival (PFS) by central review. Secondary end points included objective tumor response and disease control by central review. Results From October 2014 to January 2016, 768 patients were randomized; 765 were treated (nintedanib n = 384; placebo n = 381). Median follow-up was 13.4 months (interquartile range 11.1-15.7). OS was not improved [median OS 6.4 months with nintedanib versus 6.0 months with placebo; hazard ratio (HR), 1.01; 95% confidence interval (CI), 0.86-1.19; P = 0.8659]. There was a significant but modest increase in PFS with nintedanib versus placebo (median PFS 1.5 versus 1.4 months, respectively; HR 0.58; 95% CI 0.49-0.69; P <0.0001). There were no complete or partial responses. Adverse events (AEs) occurred in 97% of 384 nintedanib-treated patients and 93% of 381 placebo-treated patients. The most frequent grade ≥3 AEs were liver-related AEs (nintedanib 16%; placebo 8%) and fatigue (nintedanib 9%; placebo 6%). Conclusions The study failed to meet both co-primary end points. Nintedanib did not improve OS and was associated with a significant but modest increase in PFS versus placebo. Nintedanib was well tolerated. ClinicalTrials.gov number NCT02149108 (LUME-Colon 1).
Original languageEnglish
Pages (from-to)1955-1963
Number of pages9
JournalAnnals of Oncology
Volume29
Issue number9
DOIs
Publication statusPublished - Sep 1 2018

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Colonic Neoplasms
Colorectal Neoplasms
Placebos
Disease-Free Survival
Therapeutics
Survival
nintedanib
Confidence Intervals
Random Allocation
Fatigue
Disease Progression
Colon
Adenocarcinoma
Radiotherapy
Neoplasm Metastasis
Safety
Liver
Growth

Keywords

  • angiogenesis inhibition, chemorefractory metastatic colorectal cancer, nintedanib

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Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1): A phase III, international, randomized, placebo-controlled study. / Van Cutsem, E.; Yoshino, T.; Lenz, H. J.; Lonardi, S.; Falcone, A.; Limón, M. L.; Saunders, M.; Sobrero, A.; Park, Y. S.; Ferreiro, R.; Hong, Y. S.; Tomasek, J.; Taniguchi, H.; Ciardiello, F.; Stoehr, J.; Oum'hamed, Z.; Vlassak, S.; Studeny, M.; Argiles, G.

In: Annals of Oncology, Vol. 29, No. 9, 01.09.2018, p. 1955-1963.

Research output: Contribution to journalArticle

Van Cutsem, E, Yoshino, T, Lenz, HJ, Lonardi, S, Falcone, A, Limón, ML, Saunders, M, Sobrero, A, Park, YS, Ferreiro, R, Hong, YS, Tomasek, J, Taniguchi, H, Ciardiello, F, Stoehr, J, Oum'hamed, Z, Vlassak, S, Studeny, M & Argiles, G 2018, 'Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1): A phase III, international, randomized, placebo-controlled study', Annals of Oncology, vol. 29, no. 9, pp. 1955-1963. https://doi.org/10.1093/annonc/mdy241
Van Cutsem, E. ; Yoshino, T. ; Lenz, H. J. ; Lonardi, S. ; Falcone, A. ; Limón, M. L. ; Saunders, M. ; Sobrero, A. ; Park, Y. S. ; Ferreiro, R. ; Hong, Y. S. ; Tomasek, J. ; Taniguchi, H. ; Ciardiello, F. ; Stoehr, J. ; Oum'hamed, Z. ; Vlassak, S. ; Studeny, M. ; Argiles, G. / Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1): A phase III, international, randomized, placebo-controlled study. In: Annals of Oncology. 2018 ; Vol. 29, No. 9. pp. 1955-1963.
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abstract = "Background Angiogenesis is critical to colorectal cancer (CRC) growth and metastasis. Phase I/II studies have demonstrated the efficacy of nintedanib, a triple angiokinase inhibitor, in patients with metastatic CRC. This global, randomized, phase III study investigated the efficacy and safety of nintedanib in patients with refractory CRC after failure of standard therapies. Patients and methods Eligible patients (Eastern Cooperative Oncology Group performance status 0-1, with histologically/cytologically confirmed metastatic/locally advanced CRC adenocarcinoma unamenable to surgery and/or radiotherapy) were randomized 1: 1 to receive nintedanib (200 mg twice daily) or placebo (twice daily), until disease progression or undue toxicity. Patients were stratified by previous regorafenib, time from onset of metastatic disease to randomization, and region. Co-primary end points were overall survival (OS) and progression-free survival (PFS) by central review. Secondary end points included objective tumor response and disease control by central review. Results From October 2014 to January 2016, 768 patients were randomized; 765 were treated (nintedanib n = 384; placebo n = 381). Median follow-up was 13.4 months (interquartile range 11.1-15.7). OS was not improved [median OS 6.4 months with nintedanib versus 6.0 months with placebo; hazard ratio (HR), 1.01; 95{\%} confidence interval (CI), 0.86-1.19; P = 0.8659]. There was a significant but modest increase in PFS with nintedanib versus placebo (median PFS 1.5 versus 1.4 months, respectively; HR 0.58; 95{\%} CI 0.49-0.69; P <0.0001). There were no complete or partial responses. Adverse events (AEs) occurred in 97{\%} of 384 nintedanib-treated patients and 93{\%} of 381 placebo-treated patients. The most frequent grade ≥3 AEs were liver-related AEs (nintedanib 16{\%}; placebo 8{\%}) and fatigue (nintedanib 9{\%}; placebo 6{\%}). Conclusions The study failed to meet both co-primary end points. Nintedanib did not improve OS and was associated with a significant but modest increase in PFS versus placebo. Nintedanib was well tolerated. ClinicalTrials.gov number NCT02149108 (LUME-Colon 1).",
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TY - JOUR

T1 - Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1): A phase III, international, randomized, placebo-controlled study

AU - Van Cutsem, E.

AU - Yoshino, T.

AU - Lenz, H. J.

AU - Lonardi, S.

AU - Falcone, A.

AU - Limón, M. L.

AU - Saunders, M.

AU - Sobrero, A.

AU - Park, Y. S.

AU - Ferreiro, R.

AU - Hong, Y. S.

AU - Tomasek, J.

AU - Taniguchi, H.

AU - Ciardiello, F.

AU - Stoehr, J.

AU - Oum'hamed, Z.

AU - Vlassak, S.

AU - Studeny, M.

AU - Argiles, G.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background Angiogenesis is critical to colorectal cancer (CRC) growth and metastasis. Phase I/II studies have demonstrated the efficacy of nintedanib, a triple angiokinase inhibitor, in patients with metastatic CRC. This global, randomized, phase III study investigated the efficacy and safety of nintedanib in patients with refractory CRC after failure of standard therapies. Patients and methods Eligible patients (Eastern Cooperative Oncology Group performance status 0-1, with histologically/cytologically confirmed metastatic/locally advanced CRC adenocarcinoma unamenable to surgery and/or radiotherapy) were randomized 1: 1 to receive nintedanib (200 mg twice daily) or placebo (twice daily), until disease progression or undue toxicity. Patients were stratified by previous regorafenib, time from onset of metastatic disease to randomization, and region. Co-primary end points were overall survival (OS) and progression-free survival (PFS) by central review. Secondary end points included objective tumor response and disease control by central review. Results From October 2014 to January 2016, 768 patients were randomized; 765 were treated (nintedanib n = 384; placebo n = 381). Median follow-up was 13.4 months (interquartile range 11.1-15.7). OS was not improved [median OS 6.4 months with nintedanib versus 6.0 months with placebo; hazard ratio (HR), 1.01; 95% confidence interval (CI), 0.86-1.19; P = 0.8659]. There was a significant but modest increase in PFS with nintedanib versus placebo (median PFS 1.5 versus 1.4 months, respectively; HR 0.58; 95% CI 0.49-0.69; P <0.0001). There were no complete or partial responses. Adverse events (AEs) occurred in 97% of 384 nintedanib-treated patients and 93% of 381 placebo-treated patients. The most frequent grade ≥3 AEs were liver-related AEs (nintedanib 16%; placebo 8%) and fatigue (nintedanib 9%; placebo 6%). Conclusions The study failed to meet both co-primary end points. Nintedanib did not improve OS and was associated with a significant but modest increase in PFS versus placebo. Nintedanib was well tolerated. ClinicalTrials.gov number NCT02149108 (LUME-Colon 1).

AB - Background Angiogenesis is critical to colorectal cancer (CRC) growth and metastasis. Phase I/II studies have demonstrated the efficacy of nintedanib, a triple angiokinase inhibitor, in patients with metastatic CRC. This global, randomized, phase III study investigated the efficacy and safety of nintedanib in patients with refractory CRC after failure of standard therapies. Patients and methods Eligible patients (Eastern Cooperative Oncology Group performance status 0-1, with histologically/cytologically confirmed metastatic/locally advanced CRC adenocarcinoma unamenable to surgery and/or radiotherapy) were randomized 1: 1 to receive nintedanib (200 mg twice daily) or placebo (twice daily), until disease progression or undue toxicity. Patients were stratified by previous regorafenib, time from onset of metastatic disease to randomization, and region. Co-primary end points were overall survival (OS) and progression-free survival (PFS) by central review. Secondary end points included objective tumor response and disease control by central review. Results From October 2014 to January 2016, 768 patients were randomized; 765 were treated (nintedanib n = 384; placebo n = 381). Median follow-up was 13.4 months (interquartile range 11.1-15.7). OS was not improved [median OS 6.4 months with nintedanib versus 6.0 months with placebo; hazard ratio (HR), 1.01; 95% confidence interval (CI), 0.86-1.19; P = 0.8659]. There was a significant but modest increase in PFS with nintedanib versus placebo (median PFS 1.5 versus 1.4 months, respectively; HR 0.58; 95% CI 0.49-0.69; P <0.0001). There were no complete or partial responses. Adverse events (AEs) occurred in 97% of 384 nintedanib-treated patients and 93% of 381 placebo-treated patients. The most frequent grade ≥3 AEs were liver-related AEs (nintedanib 16%; placebo 8%) and fatigue (nintedanib 9%; placebo 6%). Conclusions The study failed to meet both co-primary end points. Nintedanib did not improve OS and was associated with a significant but modest increase in PFS versus placebo. Nintedanib was well tolerated. ClinicalTrials.gov number NCT02149108 (LUME-Colon 1).

KW - angiogenesis inhibition, chemorefractory metastatic colorectal cancer, nintedanib

U2 - 10.1093/annonc/mdy241

DO - 10.1093/annonc/mdy241

M3 - Article

VL - 29

SP - 1955

EP - 1963

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 9

ER -