{"entity":{"id":"cabozantinib","kind":"drug","name":"Cabozantinib","aka":[],"tldr":"A pill that blocks both blood-vessel growth and the MET escape pathway, used in kidney, liver, thyroid and, since 2025, neuroendocrine cancers.","summary":"CELESTIAL: OS 10.2 vs 8.0 months after sorafenib in HCC (HR 0.76). CheckMate 9ER: with nivolumab, first-line RCC. CABINET (2024-25): PFS 13.8 vs 4.4 months in pancreatic NETs and 8.4 vs 3.9 months in extra-pancreatic NETs after prior therapy, leading to FDA approval in March 2025; ESMO 2025 subgroup showed an 81% reduction in progression risk in lung and thymic NETs. COSMIC-312 (with atezolizumab, first-line HCC) improved PFS but not OS.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Cabozantinib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Cabozantinib"}],"tags":[],"related":[],"cancers":["hcc","hcc-advanced","rcc","neuroendocrine","thyroid","medullary-thyroid-cancer","clear-cell-rcc","papillary-rcc"],"sections":[],"technologies":["kinase-inhibitors","antiangiogenic"],"targets":["met","vegf","ret"],"drugs":[],"companies":["exelixis","ipsen"],"institutions":[],"pathways":[],"terms":[],"trials":["celestial","cabinet","nct03755791","nct04446117","nct03690388","nct07011719","nct03634540","nct07293351","nct03899155","nct04586231","nct07405164","checkmate-9er","cosmic-313","contact-03"],"people":[],"bottlenecks":[],"keyPapers":["paper-exam-cabozantinib-mtc-elisei-jco-2013","paper-papmet-pal-lancet-2021"],"journals":[],"dependsOn":[],"notes":["In kidney cancer: CABOSUN (first line versus sunitinib, PFS benefit), METEOR (second line versus everolimus, OS 21.4 versus 16.5 months), CheckMate 9ER (with nivolumab, OS benefit), COSMIC-313 (triplet, no OS gain) and CONTACT-03 (no benefit from adding atezolizumab). The dose is 40 mg daily with nivolumab, and about 65 percent of patients have a grade 3 or higher event; the long half-life of about 99 hours matters when toxicity appears."],"brand":"Cabometyx","modality":"Small-molecule multi-kinase inhibitor (MET, VEGFR2, AXL, RET)","mechanism":"Oral inhibitor of MET, VEGFR2, AXL, RET, KIT and FLT3; MET/AXL inhibition counters anti-VEGF resistance.","approvals":[{"region":"US","year":2012,"indication":"Medullary thyroid cancer (Cometriq)"},{"region":"US","year":2016,"indication":"Advanced RCC"},{"region":"US","year":2019,"indication":"HCC previously treated with sorafenib"},{"region":"US","year":2025,"indication":"Advanced pancreatic and extra-pancreatic neuroendocrine tumours after prior therapy (CABINET)"},{"region":"US","year":2017,"indication":"First-line advanced RCC (CABOSUN)"},{"region":"US","year":2021,"indication":"First-line advanced RCC with nivolumab (CheckMate 9ER)"},{"region":"EU","year":2014,"indication":"Cometriq for medullary thyroid cancer; 21 Mar 2014. Cabometyx (RCC) Sep 2016"}],"mechanismSteps":["Blocks VEGFR2 on endothelium","Blocks MET and AXL, which tumours upregulate under hypoxia to escape anti-VEGF therapy","Reduces invasion and metastasis signalling"],"dosing":{"route":"Oral","schedule":"60 mg daily (Cabometyx tablets)","modifications":"40 mg then 20 mg for intolerance","monitoring":"Blood pressure, liver enzymes, wound healing"},"toxicity":[{"event":"Hand-foot skin reaction","anyGradePct":46,"grade3PlusPct":17,"note":"CELESTIAL"},{"event":"Hypertension","anyGradePct":29,"grade3PlusPct":16,"note":"CELESTIAL"},{"event":"Diarrhoea","anyGradePct":54,"grade3PlusPct":10,"note":"CELESTIAL"}],"access":[],"regulatoryEvents":[{"date":"2025-03-26","type":"approval","region":"US","note":"NET indication on CABINET","source":"https://www.ncf.net/post/2025-highlights-in-neuroendocrine-cancer"}]},"route":"/drugs/cabozantinib/","neighbours":{"cancer":[{"id":"adrenocortical","kind":"cancer","name":"Adrenocortical carcinoma","route":"/cancers/adrenocortical/"},{"id":"advanced-adrenocortical-carcinoma","kind":"cancer","name":"Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable)","route":"/cancers/advanced-adrenocortical-carcinoma/"},{"id":"hcc-advanced","kind":"cancer","name":"Advanced hepatocellular carcinoma (BCLC C)","route":"/cancers/hcc-advanced/"},{"id":"chromophobe-rcc","kind":"cancer","name":"Chromophobe renal cell carcinoma","route":"/cancers/chromophobe-rcc/"},{"id":"clear-cell-rcc","kind":"cancer","name":"Clear cell renal cell carcinoma","route":"/cancers/clear-cell-rcc/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"lung-net","kind":"cancer","name":"Lung neuroendocrine tumours (typical and atypical carcinoid)","route":"/cancers/lung-net/"},{"id":"medullary-thyroid-cancer","kind":"cancer","name":"Medullary thyroid cancer","route":"/cancers/medullary-thyroid-cancer/"},{"id":"metastatic-ppgl","kind":"cancer","name":"Metastatic pheochromocytoma and paraganglioma","route":"/cancers/metastatic-ppgl/"},{"id":"multiple-endocrine-neoplasia","kind":"cancer","name":"Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)","route":"/cancers/multiple-endocrine-neoplasia/"},{"id":"men2-syndrome","kind":"cancer","name":"Multiple endocrine neoplasia type 2 (MEN2A and MEN2B)","route":"/cancers/men2-syndrome/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"osteosarcoma","kind":"cancer","name":"Osteosarcoma","route":"/cancers/osteosarcoma/"},{"id":"pancreatic-net","kind":"cancer","name":"Pancreatic neuroendocrine tumours","route":"/cancers/pancreatic-net/"},{"id":"papillary-rcc","kind":"cancer","name":"Papillary renal cell 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inhibitors","route":"/technologies/kinase-inhibitors/"},{"id":"thyroid-cancer-markers","kind":"technology","name":"Thyroglobulin, calcitonin and CEA in thyroid cancer follow-up","route":"/technologies/thyroid-cancer-markers/"}],"target":[{"id":"axl","kind":"target","name":"AXL","route":"/targets/axl/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"},{"id":"ret","kind":"target","name":"RET","route":"/targets/ret/"},{"id":"ron","kind":"target","name":"RON receptor (MST1R)","route":"/targets/ron/"},{"id":"tie2","kind":"target","name":"TIE2 receptor (TEK)","route":"/targets/tie2/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"company":[{"id":"exelixis","kind":"company","name":"Exelixis","route":"/companies/exelixis/"},{"id":"ipsen","kind":"company","name":"Ipsen","route":"/companies/ipsen/"}],"trial":[{"id":"nct03729245","kind":"trial","name":"A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)","route":"/trials/nct03729245/"},{"id":"nct03690388","kind":"trial","name":"A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Va","route":"/trials/nct03690388/"},{"id":"nct05859217","kind":"trial","name":"A Study of Combining Cabozantinib and Atezolizumab for Advanced/Metastatic NSCLC (Cabatezo-1)","route":"/trials/nct05859217/"},{"id":"nct07293351","kind":"trial","name":"A Study to Evaluate the Safety, Tolerability, and Efficacy of Pumitamig Alone or in Combination With Other Agents in Participants With Advanced Renal ","route":"/trials/nct07293351/"},{"id":"nct03634540","kind":"trial","name":"A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003)","route":"/trials/nct03634540/"},{"id":"cabinet","kind":"trial","name":"CABINET (Alliance A021602)","route":"/trials/cabinet/"},{"id":"cabone","kind":"trial","name":"CABONE","route":"/trials/cabone/"},{"id":"nct01639508","kind":"trial","name":"Cabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer and Those With Other Genotypes: ROS1 or NTRK Fusions or Increased MET or A","route":"/trials/nct01639508/"},{"id":"nct03539822","kind":"trial","name":"Cabozantinib Plus Durvalumab With or Without Tremelimumab in Patients With Gastroesophageal Cancer and Other Gastrointestinal Malignancies","route":"/trials/nct03539822/"},{"id":"celestial","kind":"trial","name":"CELESTIAL","route":"/trials/celestial/"},{"id":"checkmate-9er","kind":"trial","name":"CheckMate 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S1500)","route":"/trials/papmet/"},{"id":"nct04446117","kind":"trial","name":"Study of Cabozantinib in Combination With Atezolizumab Versus Second NHT in Subjects With mCRPC","route":"/trials/nct04446117/"},{"id":"nct03755791","kind":"trial","name":"Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Participants With Advanced Hepatocellular Carcinoma (HCC) Who Have Not Rece","route":"/trials/nct03755791/"},{"id":"nct07011719","kind":"trial","name":"Study of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma","route":"/trials/nct07011719/"}],"paper":[{"id":"paper-litespark-011-motzer-lancet-2026","kind":"paper","name":"Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial","route":"/key-papers/paper-litespark-011-motzer-lancet-2026/"},{"id":"paper-cabinet-cabozantinib-nejm-2024","kind":"paper","name":"CABINET (Alliance A021602): cabozantinib for advanced neuroendocrine tumours","route":"/key-papers/paper-cabinet-cabozantinib-nejm-2024/"},{"id":"paper-exam-cabozantinib-mtc-elisei-jco-2013","kind":"paper","name":"EXAM: cabozantinib in progressive medullary thyroid cancer","route":"/key-papers/paper-exam-cabozantinib-mtc-elisei-jco-2013/"},{"id":"paper-papmet-pal-lancet-2021","kind":"paper","name":"PAPMET (SWOG 1500): cabozantinib versus sunitinib for metastatic papillary renal cell carcinoma","route":"/key-papers/paper-papmet-pal-lancet-2021/"}],"pairing":[{"id":"io-rechallenge-caution-rcc","kind":"pairing","name":"Caution: PD-1 rechallenge after progression on immunotherapy (RCC)","route":"/pairings/io-rechallenge-caution-rcc/"},{"id":"risk-directed-first-line-rcc","kind":"pairing","name":"IMDC risk → first-line regimen choice (RCC)","route":"/pairings/risk-directed-first-line-rcc/"}],"person":[{"id":"toni-choueiri","kind":"person","name":"Toni K. Choueiri","route":"/people/toni-choueiri/"}],"term":[{"id":"antiangiogenic-toxicities","kind":"term","name":"Anti-VEGF class toxicities (hypertension, proteinuria, bleeding, perforation)","route":"/terms/antiangiogenic-toxicities/"},{"id":"hand-foot-syndrome","kind":"term","name":"Hand-foot syndrome and hand-foot skin reaction","route":"/terms/hand-foot-syndrome/"},{"id":"tki-term","kind":"term","name":"Tyrosine kinase inhibitor (TKI)","route":"/terms/tki-term/"}],"pathway":[{"id":"hepatocellular-carcinoma-signalling","kind":"pathway","name":"Hepatocellular carcinoma (KEGG map)","route":"/pathways/hepatocellular-carcinoma-signalling/"},{"id":"renal-cell-carcinoma-signalling","kind":"pathway","name":"Renal cell carcinoma (KEGG map)","route":"/pathways/renal-cell-carcinoma-signalling/"},{"id":"angiogenic-switch","kind":"pathway","name":"The angiogenic switch & tumour vessels","route":"/pathways/angiogenic-switch/"},{"id":"thyroid-cancer-signalling","kind":"pathway","name":"Thyroid cancer (KEGG map)","route":"/pathways/thyroid-cancer-signalling/"}],"roadmap":[{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}