Anamorelin in Cancer Cachexia: Gut Microbiota Effects and CONUT Score as a Predictor of Response

Anamorelin, a ghrelin receptor agonist, increases body weight and lean body mass (LBM); however, its effects on the gut microbiota remain unclear. Furthermore, the predictive value of nutritional scores, such as the Controlling Nutritional Status (CONUT) score, for anamorelin response is not established. This study aimed to evaluate the effects of anamorelin on body weight, quality of life (QOL), and gut microbiota in patients with advanced cancer and cachexia, and to clarify the predictive role of nutritional indicators.

This single-center prospective observational study enrolled cachectic patients (non-small cell lung, pancreatic, gastric, or colorectal cancer) receiving anamorelin 100 mg/day with dietary counseling. Outcomes included change in body weight (baseline, 3, 6, 12 weeks), QOL (EORTC QLQ-C15-PAL), and gut microbiota diversity. The association between the baseline CONUT score and weight gain (>0 kg at 6 weeks) was analyzed.

Sixteen patients were analyzed. Body weight significantly increased from baseline at weeks 3, 6, and 12 (mean change at 12 weeks: +2.61±0.72 kg, p=0.008). In the eight patients assessed for QOL, the overall scale showed no significant change. The score for appetite loss (Q8) was 2.125±0.835 at 0 weeks vs. 1.375±0.744 at 6 weeks (unadjusted p=0.033). Gut microbiota alpha and beta diversity showed no significant change. A high baseline CONUT score (≥5) was associated with failure to gain weight in six weeks compared to a score <5 (87.5% of non-gainers had a high score vs. 12.5%; unadjusted p=0.01).

In this pilot study, anamorelin significantly increased body weight and suggested an improvement in appetite in patients with cancer and cachexia. No significant changes in overall QOL or gut microbiota diversity were detected at 6 weeks. The finding that a high baseline CONUT score may predict a lack of short-term weight gain warrants further investigation.