Anamorelin Efficacy in Non–Small‐Cell Lung Cancer Patients With Cachexia: Insights From ROMANA 1 and ROMANA 2
Barry Laird, Richard J. E. Skipworth, Philip Bonomi, Marie Fallon, Stein Kaasa, R. Giorgino, Donald C. McMillan, David C. Currow
Abstract
ABSTRACT Background Cancer cachexia presents a significant challenge, but the ghrelin agonist anamorelin shows promise as a potential treatment. This study examined whether the baseline systemic inflammatory response (SIR) (measured by the modified Glasgow Prognostic Score [mGPS]), low BMI or greater weight loss, was associated with a differential treatment effect of anamorelin in people with cachexia and non–small‐cell lung cancer (NSCLC). Methods ROMANA 1 and ROMANA 2 were double‐blind, placebo‐controlled, randomised Phase 3 trials that enrolled people with inoperable stage III/IV NSCLC with cachexia (≥ 5% weight loss within 6 months or body mass index [BMI] < 20 kg/m 2 ). Patients were randomised 2:1 to anamorelin 100 mg once daily or placebo, for 12 weeks. This is a post hoc analysis of efficacy endpoints (body weight and body composition: lean body mass [LBM] and fat mass [FM]), stratified by baseline mGPS, BMI and weight loss and measured in the modified intent‐to‐treat pooled population. Results Seven hundred ninety‐five patients had available data. Anamorelin improved body weight ( p < 0.001) and body composition parameters (LBM and FM, p < 0.01) in all mGPS groups. In patients with mGPS = 2, anamorelin increased weight > 5% and improved hand grip strength (HGS) and the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Subscale (FAACT A/CS). In patients with BMI < 20 kg/m 2 at baseline or weight loss ≥ 10% in the prior 6 months, anamorelin led to significant increases in body weight from baseline ( p < 0.001) versus placebo. Patients with weight loss ≥ 10% in the prior 6 months showed the highest improvements in LBM ( p < 0.001). Patients with BMI < 20 kg/m 2 at baseline showed the highest improvements in FM ( p < 0.001). Conclusion Anamorelin improved body composition parameters in all patients, as well as physical function and symptom burden, particularly in patients with systemic inflammation, BMI < 20 kg/m 2 and weight loss ≥ 10%. These results highlight that the anabolic mechanisms of anamorelin are more effective in high‐risk groups. Trial Registration NCT identifiers: ROMANA 1: NCT01387269; ROMANA 2: NCT01387282.