Evaluation of quality of life from a phase II study of anamorelin HCl in NSCLC patients.

Abstract

42 Background: Anamorelin HCl (ANA) is an oral ghrelin receptor agonist in development for non-small cell lung cancer (NSCLC)-associated anorexia/cachexia. Cancer cachexia is a multifactorial syndrome, characterized by decreased body weight and muscle, and worsened survival and quality of life (QoL). Here we present Phase II data, including an evaluation of QoL using the MD Anderson Symptom Inventory (MDASI) to assess severity of core symptoms in cancer patients and their impact on daily life. Methods: An international, randomized, double-blind, placebo-controlled, 12-week Phase II trial (NCT00622193) enrolled 226 Stage IIIB/IV NSCLC patients (N=76 for 50 mg ANA; N=73 for 100 mg ANA; N=77 for placebo [PL]). Co-primary endpoints were body weight and handgrip strength (HGS); safety was also assessed. QoL by MDASI was a secondary endpoint; a negative change in MDASI score represents improvement. Assessments were performed at baseline and approximately every 3 weeks over the 12-week treatment period. Results: MDASI total and domain scores improved with 100 mg ANA vs PL, although these changes were not statistically significant (mean±SE change from baseline at Week 12 for 100 mg ANA vs PL was -8.6±4.58 vs -1.5±3.29 for total score; -6.7±2.98 vs -2.9±2.24 for symptom domain score; and -1.9±1.99 vs 1.5±1.39 for interference domain score). Seven individual MDASI symptom/interference items most improved in the 100 mg ANA vs PL group were fatigue, nausea, work around the house, disturbed sleep, distressed, general activity, and mood. Over 12 weeks, ANA also significantly increased body weight vs PL (mean change from baseline was 0.14 kg, -0.3 kg, and -1.32 kg for 100 mg ANA, 50 mg ANA, and PL, respectively [p=0.0005]), and directional (non-significant) changes in HGS were also noted for both active arms vs PL. ANA was safe and well-tolerated, with less adverse events of fatigue, anorexia, and nausea reported in ANA vs PL patients. Conclusions: In this study, ANA significantly increased body weight, improved HGS and QoL, and had an overall favorable safety/tolerability profile. MDASI individual item changes demonstrated improvements in key cancer-related symptoms including fatigue, and were consistent with the adverse event profile. Clinical trial information: NCT00622193.