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

Abstract

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.

CLINICAL TRIAL REGISTRATION NUMBERS:

ROMANA 1 (NCT01387269), ROMANA 2 (NCT01387282), and ROMANA 3 (NCT01395914).

• Authors: D Currow, J S Temel, A Abernethy, J Milanowski, J Friend, K C Fearon
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 28 Issue 8 Pg. 1949-1956 (Aug 01 2017) ISSN: 1569-8041 [Electronic] England
• PMID: 28472437 (Publication Type: Clinical Trial, Phase III, Journal Article)
• Copyright: © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Chemical References

• Hydrazines
• Oligopeptides
• Placebos
• Receptors, Ghrelin
• anamorelin

Topics

• Aged
• Cachexia (drug therapy, etiology)
• Carcinoma, Non-Small-Cell Lung (complications, drug therapy, pathology)
• Double-Blind Method
• Female
• Humans
• Hydrazines (adverse effects, therapeutic use)
• Lung Neoplasms (complications, drug therapy, pathology)
• Male
• Middle Aged
• Oligopeptides (adverse effects, therapeutic use)
• Placebos
• Receptors, Ghrelin (agonists)