Advancements of investigational agents for cancer cachexia: what clinical progress have we seen in the last 5 years?

INTRODUCTION: Cancer cachexia is a multifactorial syndrome affecting up to 80% of advanced cancer patients, associated with poor quality of life, increased cancer-treatment toxicity, and reduced survival. Despite its clinical burden, no FDA- or EMA-approved pharmacologic therapies currently exist.

AREAS COVERED: This review covers key investigational therapies developed over the past five years, with a focus on agents targeting Growth Differentiation Factor 15 (GDF-15), including ponsegromab, AV-380, and NGM120. Additional agents include ghrelin receptor agonists (e.g. anamorelin), anabolic/catabolic modulators (ACM-001), and cannabinoids (ART27.13). The evolving role of low-dose olanzapine is also discussed in the 2023 ASCO guideline update. Advancements in early detection, including AI-driven biomarker models and the use of circulating miRNAs, are discussed.

EXPERT OPINION: Targeting GDF-15 represents a paradigm shift in cancer cachexia treatment, with ponsegromab leading the pipeline and entering Phase 3 trials. Anamorelin has demonstrated clinical utility in improving appetite and body weight. Despite recent progress, cancer cachexia undoubtedly represents a still clinically unmet need in everyday routine praxis. The lack of standardized endpoints, heterogeneity of the syndrome, and absence of FDA-approved treatments remain major barriers to treatment implementation. Multimodal strategies combining pharmacological treatment with nutritional and rehabilitative support are likely to define future therapeutic success.