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 pancre...
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| Format: | Article |
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Wiley
2018
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| Online Access: | https://eprints.nottingham.ac.uk/52403/ |
| _version_ | 1848798718022647808 |
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| 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 |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| 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 (OS).
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 OS: the hazard ratio (HR) was 1.70 (90% confidence interval, 1.1–2.7) for 300 mg versus placebo and 1.3 (0.82–2.1) for 100 mg versus placebo (recommended doses). Progression-free survival results were consistent with the OS results. A numerically higher HR 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 versus patients with ≥5% WL. Among possibly drug-related adverse events, fatigue, diarrhea, and anorexia were more common in LY2495655- 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). |
| first_indexed | 2025-11-14T20:24:13Z |
| format | Article |
| id | nottingham-52403 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:24:13Z |
| publishDate | 2018 |
| publisher | Wiley |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-524032024-08-15T15:30:48Z https://eprints.nottingham.ac.uk/52403/ 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. 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 (OS). 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 OS: the hazard ratio (HR) was 1.70 (90% confidence interval, 1.1–2.7) for 300 mg versus placebo and 1.3 (0.82–2.1) for 100 mg versus placebo (recommended doses). Progression-free survival results were consistent with the OS results. A numerically higher HR 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 versus patients with ≥5% WL. Among possibly drug-related adverse events, fatigue, diarrhea, and anorexia were more common in LY2495655- 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). Wiley 2018-07-27 Article PeerReviewed Golan, Talia, Geva, Ravit, Richards, Donald, Madhusudan, Srinivasan, Lin, Boris Kin, Wang, Haofei Tiffany, Walgren, Richard A. and Stemmer, Salomon M. (2018) LY2495655, an antimyostatin antibody in pancreatic cancer: a randomized phase 2 trial. Journal of Cachexia, Sarcopenia and Muscle . ISSN 2190-6009 Myostatin; Cachexia; Pancreatic cancer; Muscle mass https://onlinelibrary.wiley.com/doi/abs/10.1002/jcsm.12331 doi:10.1002/jcsm.12331 doi:10.1002/jcsm.12331 |
| spellingShingle | Myostatin; Cachexia; Pancreatic cancer; Muscle mass 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 | Myostatin; Cachexia; Pancreatic cancer; Muscle mass |
| url | https://eprints.nottingham.ac.uk/52403/ https://eprints.nottingham.ac.uk/52403/ https://eprints.nottingham.ac.uk/52403/ |