ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia

Currow, David; Temel, J. S.; Abernethy, A.; Milanowski, J.; Friend, J.; Fearon, K. C.

Abstract

© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Background: Cancer anorexia-cachexia is a debilitating condition frequently observed in NSCLC patients, characterized by decreased body weight, reduced food intake, and impaired quality of life. Anamorelin, a novel selective ghrelin receptor agonist, has anabolic and appetite-enhancing activities. Patients and methods: ROMANA 3 was a safety extension study of two phase 3, double-blind studies that assessed safety and efficacy of anamorelin in advanced NSCLC patients with cachexia. Patients with preserved Eastern Cooperative Oncology Group ≤ 2 after completing 12 weeks (w) on the ROMANA 1 or ROMANA 2 trials (0-12 weeks) could enroll in ROMANA 3 and continue to receive anamorelin 100 mg or placebo once daily for an additional 12w (12-24 weeks). The primary endpoint of ROMANA 3 was anamorelin safety/tolerability (12-24 weeks). Secondary endpoints included changes in body weight, handgrip strength (HGS), and symptom burden (0-24 weeks). Results: Of the 703 patients who completed ROMANA 1 and ROMANA 2, 513 patients entered ROMANA 3 (anamorelin, N = 345, mean age 62.0 years; placebo, N = 168; mean age 62.2 years). During ROMANA 3, anamorelin and placebo groups had similar incidences of treatment-emergent adverse events (TEAEs; 52.2% versus 55.7%), grade ≥ 3 TEAEs (22.4% versus 21.6%), and serious TEAEs (12.8% versus 12.6%). There were 36 (10.5%) and 23 (13.8%) deaths in the anamorelin and placebo groups, respectively; none were drug-related. Improvements in body weight and anorexia-cachexia symptoms observed in the original trials were consistently maintained over 12-24 weeks. Anamorelin, versus placebo, significantly increased body weight from baseline of original trials at all time points (P < 0.0001) and improved anorexia-cachexia symptoms at weeks 3, 6, 9, 12, and 16 (P < 0.05). No significant improvement in HGS was seen in either group. Conclusion: During the 12-24 weeks ROMANA 3 trial, anamorelin continued to be well tolerated. Over the entire 0-24w treatment period, body weight and symptom burden were improved with anamorelin.

Citation

Currow, D., Temel, J. S., Abernethy, A., Milanowski, J., Friend, J., & Fearon, K. C. (2017). ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 28(8), 1949-1956. https://doi.org/10.1093/annonc/mdx192

• Journal Article Type: Article
• Online Publication Date: Jan 7, 2020
• Publication Date: Aug 1, 2017
• Deposit Date: Apr 9, 2019
• Publicly Available Date: Oct 27, 2022
• Journal: Annals of Oncology
• Print ISSN: 0923-7534
• Electronic ISSN: 1569-8041
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 28
• Issue: 8
• Pages: 1949-1956
• DOI: https://doi.org/10.1093/annonc/mdx192
• Keywords: ROMANA 3; Anamorelin; Non-small-cell lung cancer; Body weight; Anorexia–cachexia symptoms; ROMANA 1 and ROMANA 2
• Public URL: https://hull-repository.worktribe.com/output/1563334
• Publisher URL: https://academic.oup.com/annonc/article/28/8/1949/3796493