{"entity":{"id":"paper-groarke-ponsegromab-cancer-cachexia-nejm-2024","kind":"paper","name":"Ponsegromab for the Treatment of Cancer Cachexia","aka":[],"tldr":"The 2024 phase 2 trial in which an antibody blocking the hormone GDF-15 helped patients with cancer-related wasting, a third of them with pancreatic cancer, gain about two to three kilograms in twelve weeks and become more active.","summary":"Groarke and colleagues randomised 187 patients with cancer cachexia and serum GDF-15 of 1,500 pg per millilitre or more (40 percent non-small-cell lung cancer, 32 percent pancreatic cancer, 29 percent colorectal cancer) 1:1:1:1 to ponsegromab 100, 200 or 400 mg or placebo subcutaneously every four weeks for three doses in a 12-week double-blind phase 2 trial. The primary endpoint, change in body weight at 12 weeks, favoured every dose: median between-group differences of 1.22 kg (100 mg), 1.92 kg (200 mg) and 2.81 kg (400 mg; 95 percent credible interval 1.55 to 4.08). Appetite, cachexia symptoms and digitally measured physical activity improved at 400 mg. Adverse events of any cause occurred in 70 percent on ponsegromab and 80 percent on placebo. Funded by Pfizer; NCT05546476.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2409515"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39282907/"},{"label":"ClinicalTrials.gov NCT05546476","url":"https://clinicaltrials.gov/study/NCT05546476"}],"tags":["pancreatic-evidence"],"related":["paper-fearon-lancet-oncol","survivorship-roadmap"],"cancers":["pancreatic","nsclc","colorectal"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["ponsegromab"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2409515","pmid":"39282907","authors":"Groarke JD, Crawford J, Collins SM, et al.","paperType":"rct","findings":["187 patients with cachexia and raised GDF-15; 32 percent pancreatic cancer.","Weight gain versus placebo at 12 weeks: 1.22 kg (100 mg), 1.92 kg (200 mg), 2.81 kg (400 mg).","Appetite, symptoms and physical activity improved at 400 mg; adverse events 70 versus 80 percent."],"whatItMeans":"The first drug to reverse cancer cachexia mechanistically rather than by appetite stimulation, in a disease where weight loss stops chemotherapy being delivered; the phase 3 programme and the question of survival remain.","caveats":["Twelve weeks, weight as the primary endpoint; effects on treatment delivery, function and survival are not shown.","Patients were selected by high GDF-15, so the result applies to that subset."],"participants":187},"route":"/key-papers/paper-groarke-ponsegromab-cancer-cachexia-nejm-2024/","neighbours":{"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-ponsegromab-phase-2-n-engl-j-med-2024","kind":"paper","name":"Ponsegromab for the Treatment of Cancer Cachexia","route":"/key-papers/paper-ponsegromab-phase-2-n-engl-j-med-2024/"}],"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/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"section":[{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"drug":[{"id":"ponsegromab","kind":"drug","name":"Ponsegromab","route":"/drugs/ponsegromab/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"bottleneck":[{"id":"b-cachexia-supportive","kind":"bottleneck","name":"Cachexia, toxicity and the limits of the patient","route":"/bottlenecks/b-cachexia-supportive/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"id":"idea-pdac-cachexia-trials-embedded-in-chemotherapy-trials","kind":"idea","name":"Embed cachexia treatment in chemotherapy trials: weight, muscle and treatment delivery as co-primary endpoints","route":"/ideas/idea-pdac-cachexia-trials-embedded-in-chemotherapy-trials/"}]}}