1483O_PR - Anamorelin for the treatment of cancer anorexia-cachexia in NSCLC: Results from the phase 3 studies ROMANA 1 and 2

Date 27 September 2014
Event ESMO 2014
Session Supportive and palliative care
Topics Supportive Care
Lung and other Thoracic Tumours
Presenter Jennifer Temel
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors J. Temel1, D. Currow2, K. Fearon3, L. Gleich4, Y. Yan5, J. Friend5, A. Abernethy6
  • 1Departement Of Medicine, Massachusetts General Hospital, 02114-2696 - Boston/US
  • 2Palliative And Supportive Services, Flinders University, Adelaide/AU
  • 3Surgical Oncology, Western General Hospital, Edinburgh/GB
  • 4Medical Affairs, Medpace, 45227 - Cincinnati/US
  • 5R&d, Helsinn Therapeutics, Inc., Bridgewater/US
  • 6School Of Medicine, Duke Univeristy, 27710 - Durham/US

 

Abstract

Aim

Cancer anorexia-cachexia syndrome is a common debilitating condition, characterized by decreased body weight, mainly lean body mass (LBM) and negatively impacts quality of life and prognosis. Anamorelin HCl (ANAM) is a novel selective ghrelin receptor agonist with appetite-enhancing and anabolic activity.

Methods

These were two international, double-blind, Phase 3 trials assessing ANAM efficacy and safety in patients with unresectable Stage III/IV NSCLC, ECOG 0-2 and cachexia (≥5% weight loss within prior 6 months or BMI <20 kg/m2). Patients were randomized (2:1) to 100 mg ANAM or placebo, given daily orally for 12 weeks and were permitted to receive chemotherapy while on study.Co-primary endpoints were change from baseline over 12 weeks in LBM (measured by DXA) and in handgrip strength (HGS). Secondary endpoints included change in body weight and in the anorexia-cachexia subdomain of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire. Safety assessments included lab values and adverse events (AEs).

Results

There were no within-study population differences for ROMANA 1 (N = 484) and ROMANA 2 (N = 495). Over 12 weeks, ANAM significantly increased LBM vs placebo (p < 0.0001) in both studies. In ROMANA 1, median change in LBM was 1.10 kg [95% CI 0.76; 1.42] for ANAM vs -0.44 kg [95% CI -0.88; 0.20] for placebo; similarly, changes in ROMANA 2 were ANAM 0.75 kg (95% CI 0.51; 1.00) vs placebo -0.96 kg (95% CI -1.27; -0.46). Change in HGS was not statistically different between study arms. ANAM increased body weight (2.20 ± 0.3 vs 0.14 ± 0.4 kg; p < 0.0001; and 0.95 ± 0.4 vs -0.57 ± 0.4 kg; p < 0.0001) and improved FAACT subdomain scores (4.12 ± 0.8 vs 1.92 ± 0.8; p = 0.0004; and 3.48 ± 0.9 vs 1.34 ± 1.0; p = 0.0016). In the ANAM arm, most frequent drug-related AEs were hyperglycemia (5.3%) and nausea (3.8%) for ROMANA 1, hyperglycemia (4.2%) and diabetes (2.1%) for ROMANA 2. Both studies had few drug-related Grade ≥3 AEs (0.9%, 2.7%).

Conclusions

In two global, large-scale Phase 3 studies, ANAM for 12 weeks was well tolerated, and significantly improved LBM, body weight, and anorexia-cachexia symptoms/concerns in advanced NSCLC patients with cachexia.

Disclosure

K. Fearon: has received research funding from Helsinn; L. Gleich: is an employee of Medpace, Inc. Y. Yan and J. Friend: is an employee of Helsinn Therapeutics (US), Inc.; A. Abernethy: Received research funding from DARA, Celgene, Helsinn, Bristol-Myers Squibb (BMS), Dendreon, GSK, Pfizer; has consulting agreements with BMS and ACORN Research; is on the Board of Directors of athenahealth (a health information technology company).All other authors have declared no conflicts of interest.