Anamorelin in cachectic patients with non-small cell lung cancer (NSCLC) and acute phase protein reaction (APPR): Pooled analysis of two phase 3 trials (ROMANA 1 and ROMANA 2)

Abstract

Background: Cancer anorexia‐cachexia frequently occurs in NSCLC patients, may be accompanied by systemic inflammation, and results in reduced muscle/lean body mass (LBM) and decreased appetite. The randomized, phase 3, double‐blind ROMANA 1 (NCT01387269; N = 484) and ROMANA 2 (NCT01387282; N = 495) trials in cachectic NSCLC patients demonstrated that the ghrelin receptor agonist anamorelin improved LBM, body weight, fat mass (FM), and symptom burden compared with placebo, and was well tolerated. This analysis compared the efficacy of anamorelin in patients with or without an APPR (C‐reactive protein [CRP] >10 or ≤10 mg/L, respectively). Methods: Patients with stage III/IV NSCLC and cachexia (≥5% weight loss during prior 6 months or body mass index <20 kg/m2) were randomly assigned (2:1) to daily oral 100 mg anamorelin or placebo for 12 weeks. A post‐hoc analysis of pooled data from both trials evaluated changes in LBM, FM, body weight, and symptom burden (FAACT Anorexia/Cachexia Scale [A/CS]) in patients with (N = 527) or without an APPR (N = 293); treatment differences, 95% CI, and nominal p values are presented. Results: An APPR was observed at baseline in approximately 64% of patients enrolled, with similar proportions between the 2 arms and no clear difference in change from baseline in CRP over 12 weeks (anamorelin: 0.5 ± 44.4 mg/L; placebo: ‐6.8 ± 48.20 mg/ L). In anamorelin‐ vs placebo‐treated patients, consistent increases in LBM were seen both in patients with an APPR (1.55 kg [1.02‐2.07]; p < 0.001) and in those without (1.47 kg [0.84‐2.11]; p < 0.001). Consistent comparable FM increases were also seen (0.96 kg [0.43‐1.48]; p < 0.001 and 1.01 kg [0.31‐1.70]; p = 0.005, with and without an APPR, respectively). Body weight increased consistently in patients with and without an APPR (2.09 kg [1.27‐2.91]; p < 0.001 and 2.27 kg [1.26‐3.28]; p < 0.001, respectively). Improvement in A/CS symptoms was observed both in patients with an APPR (1.90 [0.15‐3.65]; p = 0.033) and those without (1.86 [‐0.22‐3.95]; p = 0.079). Conclusions: Anamorelin does not influence APPR and leads to consistent improvements in LBM, FM and A/CS symptoms of patients regardless of APPR status.