Cargando…
LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial
BACKGROUND: Cachexia is a formidable clinical challenge in pancreatic cancer. We assessed LY2495655 (antimyostatin antibody) plus standard‐of‐care chemotherapy in pancreatic cancer using cachexia status as a stratifier. METHODS: In this randomized, phase 2 trial, patients with stage II–IV pancreatic...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204586/ https://www.ncbi.nlm.nih.gov/pubmed/30051975 http://dx.doi.org/10.1002/jcsm.12331 |
_version_ | 1783366063788916736 |
---|---|
author | Golan, Talia Geva, Ravit Richards, Donald Madhusudan, Srinivasan Lin, Boris Kin Wang, Haofei Tiffany Walgren, Richard A. Stemmer, Salomon M. |
author_facet | Golan, Talia Geva, Ravit Richards, Donald Madhusudan, Srinivasan Lin, Boris Kin Wang, Haofei Tiffany Walgren, Richard A. Stemmer, Salomon M. |
author_sort | Golan, Talia |
collection | PubMed |
description | BACKGROUND: Cachexia is a formidable clinical challenge in pancreatic cancer. We assessed LY2495655 (antimyostatin antibody) plus standard‐of‐care chemotherapy in pancreatic cancer using cachexia status as a stratifier. METHODS: In this randomized, phase 2 trial, patients with stage II–IV pancreatic cancer were randomized to 300 mg LY2495655, 100 mg LY2495655, or placebo, plus physician‐choice chemotherapy from a prespecified list of standard‐of‐care regimens for first and later lines of care. Investigational treatment was continued during second‐line treatment. The primary endpoint was overall survival. RESULTS: Overall, 125 patients were randomized. In August 2014, 300 mg LY2495655 was terminated due to imbalance in death rates between the treatment arms; in January 2015, 100 mg LY2495655 treatment was terminated due to futility. LY2495655 did not improve overall survival: the hazard ratio was 1.70 (90% confidence interval, 1.1–2.7) for 300 mg vs. placebo and 1.3 (0.82–2.1) for 100 mg vs. placebo (recommended doses). Progression‐free survival results were consistent with the overall survival results. A numerically higher hazard ratio was observed in patients with weight loss (WL) of ≥5% (cachexia) than with <5% WL within 6 months before randomization. Subgroup analyses for patients stratified by WL in the 6 months preceding enrollment suggested that functional responses to LY2495655 (either dose) may have been superior in patients with <5% WL vs. patients with ≥5% WL. Among possibly drug‐related adverse events, fatigue, diarrhoea, and anorexia were more common in LY2495655‐treated than in placebo‐treated patients. CONCLUSIONS: In the intention‐to‐treat analysis, LY2495655 did not confer clinical benefit in pancreatic cancer. Our data highlight the importance of assessing survival when investigating therapeutic management of cachexia and support the use of WL as a stratifier (independent of performance status). |
format | Online Article Text |
id | pubmed-6204586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62045862018-11-05 LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial Golan, Talia Geva, Ravit Richards, Donald Madhusudan, Srinivasan Lin, Boris Kin Wang, Haofei Tiffany Walgren, Richard A. Stemmer, Salomon M. J Cachexia Sarcopenia Muscle Original Articles BACKGROUND: Cachexia is a formidable clinical challenge in pancreatic cancer. We assessed LY2495655 (antimyostatin antibody) plus standard‐of‐care chemotherapy in pancreatic cancer using cachexia status as a stratifier. METHODS: In this randomized, phase 2 trial, patients with stage II–IV pancreatic cancer were randomized to 300 mg LY2495655, 100 mg LY2495655, or placebo, plus physician‐choice chemotherapy from a prespecified list of standard‐of‐care regimens for first and later lines of care. Investigational treatment was continued during second‐line treatment. The primary endpoint was overall survival. RESULTS: Overall, 125 patients were randomized. In August 2014, 300 mg LY2495655 was terminated due to imbalance in death rates between the treatment arms; in January 2015, 100 mg LY2495655 treatment was terminated due to futility. LY2495655 did not improve overall survival: the hazard ratio was 1.70 (90% confidence interval, 1.1–2.7) for 300 mg vs. placebo and 1.3 (0.82–2.1) for 100 mg vs. placebo (recommended doses). Progression‐free survival results were consistent with the overall survival results. A numerically higher hazard ratio was observed in patients with weight loss (WL) of ≥5% (cachexia) than with <5% WL within 6 months before randomization. Subgroup analyses for patients stratified by WL in the 6 months preceding enrollment suggested that functional responses to LY2495655 (either dose) may have been superior in patients with <5% WL vs. patients with ≥5% WL. Among possibly drug‐related adverse events, fatigue, diarrhoea, and anorexia were more common in LY2495655‐treated than in placebo‐treated patients. CONCLUSIONS: In the intention‐to‐treat analysis, LY2495655 did not confer clinical benefit in pancreatic cancer. Our data highlight the importance of assessing survival when investigating therapeutic management of cachexia and support the use of WL as a stratifier (independent of performance status). John Wiley and Sons Inc. 2018-07-27 2018-10 /pmc/articles/PMC6204586/ /pubmed/30051975 http://dx.doi.org/10.1002/jcsm.12331 Text en © 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Golan, Talia Geva, Ravit Richards, Donald Madhusudan, Srinivasan Lin, Boris Kin Wang, Haofei Tiffany Walgren, Richard A. Stemmer, Salomon M. LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial |
title | LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial |
title_full | LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial |
title_fullStr | LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial |
title_full_unstemmed | LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial |
title_short | LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial |
title_sort | ly2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204586/ https://www.ncbi.nlm.nih.gov/pubmed/30051975 http://dx.doi.org/10.1002/jcsm.12331 |
work_keys_str_mv | AT golantalia ly2495655anantimyostatinantibodyinpancreaticcancerarandomizedphase2trial AT gevaravit ly2495655anantimyostatinantibodyinpancreaticcancerarandomizedphase2trial AT richardsdonald ly2495655anantimyostatinantibodyinpancreaticcancerarandomizedphase2trial AT madhusudansrinivasan ly2495655anantimyostatinantibodyinpancreaticcancerarandomizedphase2trial AT linboriskin ly2495655anantimyostatinantibodyinpancreaticcancerarandomizedphase2trial AT wanghaofeitiffany ly2495655anantimyostatinantibodyinpancreaticcancerarandomizedphase2trial AT walgrenricharda ly2495655anantimyostatinantibodyinpancreaticcancerarandomizedphase2trial AT stemmersalomonm ly2495655anantimyostatinantibodyinpancreaticcancerarandomizedphase2trial |