487P - Survival and quality of life data from the ACT ONE randomised, double-blind, placebo-controlled, phase II study of espindolol for the treatment and...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Drug Development
Supportive Care
Non-Small-Cell Lung Cancer, Metastatic
Colon Cancer
Rectal Cancer
Presenter John Beadle
Citation Annals of Oncology (2014) 25 (suppl_4): iv146-iv164. 10.1093/annonc/mdu331
Authors J. Beadle1, A. Coats2, G.F. Ho3, K. Prabhash4, S. von Haeling5, R. Brown1, S. Anker5
  • 1Project Management, PsiOxus Therapeutics Ltd, OX14 4SD - Oxford/GB
  • 2Vice President, Monash University, Melbourne/AU
  • 3Clinical Oncology, Universiti Malaya Medical, Kuala Lumpur/MY
  • 4Dept. Medical Oncology, Tata Memorial Hospital Centre, Mumbai/IN
  • 5Department Of Cardiology, Charite Medical School, Berlin/DE

Abstract

Aim

Neurohormonal overactivity is implicated in the progression of cachexia and BBs are proposed as a potential therapy. Retrospective studies suggest that ß-blockers (BBs) may have a beneficial effect on survival in cancer patients but to date randomised prospective data has been lacking. These effects may depend upon the receptor specificities of the BB used and espindolol (eP) has been shown in preclinical studies to have superior effects compared to other BBs.

Methods

87 subjects with stage III or IV NSCLC or CRC who met a consensus definition of cachexia (including weight loss >5% in 12 months) were recruited. Excessive weight loss and significant pre-existing cardiac disease were exclusion criteria. Subjects were randomised 3:1:2 to high dose eP (HD = 10mg bd), low dose eP (LD = 2.5 mg bd) or placebo (P) and treated for 16 weeks. EQ-5D was assessed at days 0, 28, 55, 84 and 112. Survival was monitored to the date of last subject last visit.

Results

Baseline characteristics, tolerability, weight change and functional improvement data have all been presented previously (1).There were no statistically significant differences or trends in quality of life as measured by the EQ-5D instrument on any individual parameter, the VAS score or the EQ-5D Index (using UK TTO value set). Median overall survival was longer for treated subjects (HD = 61.0 wks; LD = 50.9 wks; P = 42.3 wks) and the % of responders (alive and without weight loss at day 112) was higher (HD = 43.33% vs P = 24%) but these differences were not statistically significant. This new data is supportive of the previously presented data showing statistically significant weight gain and functional improvement for eP treated subjects.

Conclusions

This study provides the first prospective randomised data on the effect of a BB on survival in cancer patients and is consistent with previously reported retrospective data. This new data for eP is also consistent with the previously reported data on weight gain and functional improvement in cancer cachexia patients.

Disclosure

J. Beadle: I am a Director, an office bearer, an Employee and a stock owner; A. Coats: I am a paid consultant and a stock owner; R. Brown: I am an employee and a stock owner; S. Anker: I am a paid consultant and stock owner.All other authors have declared no conflicts of interest.