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Cachexia pharmacotherapy covers three drug approaches to cancer wasting: ponsegromab, an antibody that blocks the appetite-suppressing hormone GDF-15 and is in phase 3; anamorelin, a ghrelin mimic approved only in Japan; and low-dose olanzapine, a generic tablet available everywhere that ASCO added to guidance in 2024. None has yet been shown to improve physical function.
Historic options (progestins, corticosteroids, cannabinoids) improve appetite briefly but add fat or water, not muscle, and carry thrombotic or catabolic harms. Anamorelin, an oral ghrelin receptor agonist, increased lean body mass by about 1 kg over placebo in the ROMANA 1 and 2 phase 3 trials in NSCLC (Lancet Oncology 2016) without improving handgrip strength, which led the EMA to refuse it in 2017; Japan approved it in 2021 and real-world use there is substantial. Ponsegromab, a GDF-15-neutralising antibody, increased weight by 2.8 kg versus placebo at the highest dose over 12 weeks in a 187-patient phase 2 trial in patients with elevated GDF-15 (NEJM 2024), with gains in appetite, activity and lean mass, and is in phase 2/3 in pancreatic cancer cachexia. Low-dose olanzapine (2.5 mg) improved appetite and weight in a 124-patient randomised trial at Tata Memorial (JCO 2023) and was added to ASCO guidance in 2024 as a reasonable option. The field's endpoint problem, whether weight or lean mass gains translate into function and survival, is being addressed through regulatory endpoint qualification and combination with exercise and nutrition.
GDF-15 acts on GFRAL in the hindbrain to suppress appetite and drive catabolism; ghrelin agonism stimulates growth hormone and appetite; olanzapine antagonises serotonergic and histaminergic appetite-suppressing pathways and blocks nausea.
Megestrol acetate is a hormone tablet used to ease advanced breast and womb cancer, and as a liquid to improve appetite and weight in people with cancer or AIDS-related wasting.
Query for this technology: (TITLE:"Cachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapine" OR ABSTRACT:"Cachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapine") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Cachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapine, not a curated reading list.
Shares Cachexia-directed therapy (GDF-15 blockade), Body composition (lean mass, fat mass, visceral fat), Resistance training and protein for cachexia and sarcopenia, CT body composition and sarcopenia measurement.
Shares Body composition (lean mass, fat mass, visceral fat), Resistance training and protein for cachexia and sarcopenia, CT body composition and sarcopenia measurement, Sarcopenia.
Shares Cachexia-directed therapy (GDF-15 blockade), Resistance training and protein for cachexia and sarcopenia, Sarcopenia, Cancer cachexia.
Shares Ponsegromab phase 2 in cancer cachexia, Resistance training and protein for cachexia and sarcopenia, Cachexia, toxicity and the limits of the patient, Diet, exercise and lifestyle roadmap: causes established → interventions that disappointed → exercise proven as treatment.
Shares Low-dose olanzapine for cancer anorexia (Tata Memorial), Cachexia, toxicity and the limits of the patient, Tata Memorial Centre, No incentive to repurpose cheap drugs.
Shares Body composition (lean mass, fat mass, visceral fat), CT body composition and sarcopenia measurement, Sarcopenia, Cancer cachexia.
Shares CT body composition and sarcopenia measurement, Sarcopenia, Cancer cachexia, Nutrition support and cachexia management.
Shares Ponsegromab phase 2 in cancer cachexia, Cachexia, toxicity and the limits of the patient, Supportive care and survivorship roadmap: making treatment bearable → proving it extends life → caring for tens of millions afterwards, Pfizer (incl. Seagen).