Anamorelin Efficacy in Non-Small-Cell Lung Cancer Patients With Cachexia: Insights From ROMANA 1 and ROMANA 2

Area of Science:

• Oncology
• Pharmacology
• Metabolism

Background:

• Cancer cachexia significantly impacts patients with non-small-cell lung cancer (NSCLC).
• The ghrelin agonist anamorelin demonstrates potential for treating cachexia.
• This study investigated anamorelin's efficacy based on baseline systemic inflammatory response (SIR), measured by modified Glasgow Prognostic Score (mGPS), low body mass index (BMI), and weight loss.

Purpose of the Study:

• To evaluate the differential treatment effect of anamorelin in NSCLC patients with cachexia.
• To assess if baseline SIR (mGPS), low BMI, or significant weight loss influences anamorelin's efficacy.
• To analyze anamorelin's impact on body weight and composition in cachectic NSCLC patients stratified by these risk factors.

Main Methods:

• Post hoc analysis of data from the double-blind, placebo-controlled, randomized Phase 3 ROMANA 1 and ROMANA 2 trials.
• Inclusion criteria: Inoperable stage III/IV NSCLC with cachexia (≥5% weight loss in 6 months or BMI <20 kg/m²).
• Patients received anamorelin 100 mg daily or placebo for 12 weeks; efficacy endpoints (body weight, lean body mass, fat mass) were stratified by baseline mGPS, BMI, and weight loss.

Main Results:

• Anamorelin significantly improved body weight, lean body mass (LBM), and fat mass (FM) across all mGPS groups (p<0.001 for weight, p<0.01 for LBM/FM).
• In patients with mGPS=2, anamorelin increased weight >5% and improved hand grip strength and quality of life (FAACT A/CS).
• Anamorelin demonstrated significant increases in body weight versus placebo in patients with BMI <20 kg/m² or ≥10% weight loss. Highest LBM improvements were seen with ≥10% weight loss, and highest FM improvements with BMI <20 kg/m².

Conclusions:

• Anamorelin effectively improved body composition, physical function, and symptom burden in NSCLC patients with cachexia.
• The drug's anabolic effects were particularly pronounced in high-risk patient groups, including those with systemic inflammation (mGPS=2), low BMI (<20 kg/m²), or substantial weight loss (≥10%).
• These findings suggest anamorelin is a promising therapeutic option for cachexia, especially in vulnerable patient populations.