{"entity":{"id":"b-cachexia-supportive","kind":"bottleneck","name":"Cachexia, toxicity and the limits of the patient","aka":[],"tldr":"Cancer cachexia, the muscle and fat wasting driven by tumour and host inflammatory signals, affects most patients with advanced pancreatic, gastric and lung cancer, and treatment-limiting toxicities decide what dose a patient can receive. Only Japan has an approved cachexia drug, and supportive care research gets a small share of funding relative to its effect.","summary":"Cancer cachexia, a syndrome of muscle and fat loss driven by tumour-derived and host inflammatory signals (IL-6, GDF15, activin), affects most patients with advanced pancreatic, gastric and lung cancer and is implicated in a large share of cancer deaths, yet anamorelin in Japan is the only approved drug anywhere and there is none in the US or Europe. Beyond cachexia, treatment-limiting toxicities determine what dose a patient can receive: neuropathy, cardiotoxicity, cytopenias, interstitial lung disease from ADCs, cytokine release and neurotoxicity from cell therapies, and fatigue. Supportive-care research receives a small share of funding relative to its effect on survival and quality of life, and effective interventions such as structured exercise and geriatric assessment are rarely prescribed. Treating the host is a therapeutic target in its own right.","asOf":"2026-09-08","links":[{"label":"Fearon et al., Definition and classification of cancer cachexia (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"},{"label":"Groarke et al., Ponsegromab for cancer cachexia (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2409515"},{"label":"Roeland et al., ASCO guideline on management of cancer cachexia (JCO 2020)","url":"https://doi.org/10.1200/JCO.20.00611"}],"tags":[],"related":["idea-exercise-as-adjuvant","idea-bio2-protein-plus-training-during-io","idea-bio2-remote-weight-step-monitoring"],"cancers":["pancreatic","gastric","nsclc","esophageal","head-and-neck"],"sections":["supportive-care"],"technologies":["cardio-oncology","exercise-oncology","scalp-cooling","geriatric-assessment"],"targets":[],"drugs":[],"companies":["pfizer"],"institutions":["asco","cruk"],"pathways":[],"terms":["trastuzumab-cardiotoxicity","ild","crs","icans","irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-fearon-lancet-oncol","paper-roeland-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"stage":"biology","severity":"major","metrics":[{"label":"Share of cancer deaths in which cachexia is the immediate cause (estimate)","value":"Up to 20%","source":"Argilés et al., Nature Reviews Cancer 2014","url":"https://doi.org/10.1038/nrc3829"},{"label":"Weight gain with the GDF-15 antibody ponsegromab vs placebo at 12 weeks in cancer cachexia (highest dose)","value":"+5.6% body weight difference","source":"Groarke et al., NEJM 2024","url":"https://doi.org/10.1056/NEJMoa2409515"},{"label":"Physician under-reporting of symptomatic toxicities compared with patient self-report across three randomised trials","value":"Substantial under-reporting for all six symptoms studied","source":"Di Maio et al., JCO 2015","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"causes":["Cachexia is driven by systemic inflammation and neuroendocrine signalling that tumour-directed therapy does not address.","Supportive-care trials have no patent-protected asset to fund them and attract little industry investment.","Toxicity is graded by clinicians on the CTCAE scale, which under-captures patient-experienced symptoms.","Dose-finding uses maximum tolerated dose, so many regimens start above what most patients can sustain.","Nutrition, exercise and psycho-oncology are delivered inconsistently and rarely reimbursed as oncology care."],"currentEfforts":["Pfizer's ponsegromab (anti-GDF-15) produced weight gain and improved activity in a phase 2 trial and is in phase 3.","Anamorelin (Ono) is approved in Japan for cachexia in lung, gastric, pancreatic and colorectal cancer.","The Cancer Grand Challenges CANCAN team is dissecting the neural and metabolic circuits of cachexia.","ASCO published its first cachexia management guideline in 2020, and PRO-CTCAE (NCI) provides a validated patient-reported toxicity instrument.","Cardio-oncology and exercise-oncology services (including the CHALLENGE trial of structured exercise in colon cancer) are formalising host-directed care.","Scalp cooling, biosimilar growth factors and ILD-monitoring algorithms for ADCs are reducing treatment-limiting toxicity."],"successLooksLike":"An anti-cachexia drug improves survival or function in a phase 3 trial and is approved in the US and EU; patient-reported toxicity is collected in every trial and used for dose decisions; supportive-care interventions with survival benefit are reimbursed and delivered to most eligible patients."},"route":"/bottlenecks/b-cachexia-supportive/","neighbours":{"idea":[{"id":"idea-bio2-low-dose-olanzapine-appetite","kind":"idea","name":"A cheap old tablet to restore appetite","route":"/ideas/idea-bio2-low-dose-olanzapine-appetite/"},{"id":"idea-fund-cachexia-programme","kind":"idea","name":"A dedicated programme for cachexia and treatment toxicity research","route":"/ideas/idea-fund-cachexia-programme/"},{"id":"idea-nl-dietitian-in-every-mdt","kind":"idea","name":"A dietitian in every gastrointestinal and head and neck tumour board","route":"/ideas/idea-nl-dietitian-in-every-mdt/"},{"id":"idea-tr1-aggregated-n-of-1-supportive-care","kind":"idea","name":"Aggregated single-patient crossover trials for symptom and supportive 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cachexia and sarcopenia","route":"/technologies/resistance-training-cachexia/"},{"id":"scalp-cooling","kind":"technology","name":"Scalp cooling (cold caps: DigniCap, Paxman)","route":"/technologies/scalp-cooling/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"institution":[{"id":"asco","kind":"institution","name":"American Society of Clinical Oncology (ASCO)","route":"/institutions/asco/"},{"id":"cancer-grand-challenges","kind":"institution","name":"Cancer Grand Challenges","route":"/institutions/cancer-grand-challenges/"},{"id":"cruk","kind":"institution","name":"Cancer Research UK","route":"/institutions/cruk/"},{"id":"espen","kind":"institution","name":"European Society for Clinical Nutrition and Metabolism","route":"/institutions/espen/"},{"id":"mascc","kind":"institution","name":"Multinational Association of Supportive Care in Cancer","route":"/institutions/mascc/"}],"term":[{"id":"cachexia","kind":"term","name":"Cancer cachexia","route":"/terms/cachexia/"},{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"icans","kind":"term","name":"ICANS (neurotoxicity)","route":"/terms/icans/"},{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/"},{"id":"ild","kind":"term","name":"Interstitial lung disease (ILD) / pneumonitis","route":"/terms/ild/"},{"id":"malnutrition-screening","kind":"term","name":"Malnutrition screening tools (MUST, NRS-2002, MST, PG-SGA)","route":"/terms/malnutrition-screening/"},{"id":"nutrition-impact-symptoms","kind":"term","name":"Nutrition impact symptoms","route":"/terms/nutrition-impact-symptoms/"},{"id":"sarcopenia","kind":"term","name":"Sarcopenia","route":"/terms/sarcopenia/"},{"id":"trastuzumab-cardiotoxicity","kind":"term","name":"Trastuzumab cardiotoxicity","route":"/terms/trastuzumab-cardiotoxicity/"}],"paper":[{"id":"paper-fearon-lancet-oncol","kind":"paper","name":"Definition and classification of cancer cachexia: an international consensus","route":"/key-papers/paper-fearon-lancet-oncol/"},{"id":"paper-roberts-pert-survival-pancreatic-cancer-pancreatology-2019","kind":"paper","name":"Enzyme replacement improves survival among patients with pancreatic cancer: Results of a population based study","route":"/key-papers/paper-roberts-pert-survival-pancreatic-cancer-pancreatology-2019/"},{"id":"paper-roeland-j-clin-oncol","kind":"paper","name":"Management of Cancer Cachexia: ASCO Guideline","route":"/key-papers/paper-roeland-j-clin-oncol/"},{"id":"paper-groarke-ponsegromab-cancer-cachexia-nejm-2024","kind":"paper","name":"Ponsegromab for the Treatment of Cancer Cachexia","route":"/key-papers/paper-groarke-ponsegromab-cancer-cachexia-nejm-2024/"}],"roadmap":[{"id":"chemotherapy-roadmap","kind":"roadmap","name":"Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs","route":"/roadmaps/chemotherapy-roadmap/"},{"id":"nutrition-lifestyle-roadmap","kind":"roadmap","name":"Diet, exercise and lifestyle roadmap: causes established → interventions that disappointed → exercise proven as treatment","route":"/roadmaps/nutrition-lifestyle-roadmap/"},{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"},{"id":"survivorship-roadmap","kind":"roadmap","name":"Supportive care and survivorship roadmap: making treatment bearable → proving it extends life → caring for tens of millions afterwards","route":"/roadmaps/survivorship-roadmap/"}],"trial":[{"id":"olanzapine-appetite-tmh","kind":"trial","name":"Low-dose olanzapine for cancer anorexia (Tata Memorial)","route":"/trials/olanzapine-appetite-tmh/"},{"id":"ponsegromab-phase-2","kind":"trial","name":"Ponsegromab phase 2 in cancer cachexia","route":"/trials/ponsegromab-phase-2/"},{"id":"romana-1-2","kind":"trial","name":"ROMANA 1 and ROMANA 2","route":"/trials/romana-1-2/"}]}}