{"entity":{"id":"paper-fakih-codebreak-300-sotorasib-panitumumab-nejm-2023","kind":"paper","name":"Sotorasib plus panitumumab in refractory colorectal cancer with mutated KRAS G12C (CodeBreaK 300)","aka":[],"tldr":"KRAS G12C inhibitors alone barely work in bowel cancer because the tumour switches EGFR back on. Blocking both at once more than doubled progression-free survival against standard refractory treatment.","summary":"Fakih, Salvatore, Esaki and colleagues assigned patients with chemorefractory metastatic colorectal cancer carrying a KRAS G12C mutation, who had not previously received a KRAS G12C inhibitor, to sotorasib 960 mg daily plus panitumumab (53 patients), sotorasib 240 mg daily plus panitumumab (53 patients), or the investigator's choice of trifluridine-tipiracil or regorafenib (54 patients). The primary end point was progression-free survival by blinded independent central review; key secondary end points were overall survival and objective response.\n\nKRAS G12C occurs in approximately 3 to 4 percent of patients with metastatic colorectal cancer, and monotherapy with KRAS G12C inhibitors had yielded only modest efficacy.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2308795"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37870968/"}],"tags":["colorectal-evidence"],"related":["kras-roadmap","paper-ostrem-kras-g12c-nature-2013","paper-douillard-prime-panitumumab-ras-nejm-2013"],"cancers":["colorectal","kras-g12c-colorectal"],"sections":["targeted-therapy"],"technologies":["kras-inhibitors","monoclonal-antibody"],"targets":["kras","egfr"],"drugs":["sotorasib","panitumumab","trifluridine-tipiracil","regorafenib"],"companies":["amgen"],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":["codebreak-300"],"people":[],"bottlenecks":["b-undruggable-targets","b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2308795","pmid":"37870968","authors":"Fakih MG, Salvatore L, Esaki T, et al.","paperType":"rct","findings":["At a median 7.8 months, median progression-free survival 5.6 months (95 percent CI 4.2 to 6.3) with sotorasib 960 mg plus panitumumab and 3.9 months (3.7 to 5.8) with 240 mg plus panitumumab, against 2.2 months (1.9 to 3.9) with standard care.","Hazard ratio for progression or death 0.49 (0.30 to 0.80, p=0.006) for the 960 mg combination and 0.58 (0.36 to 0.93, p=0.03) for the 240 mg combination.","Objective response 26.4 percent (15.3 to 40.3), 5.7 percent (1.2 to 15.7) and 0 percent (0.0 to 6.6) respectively.","Treatment-related grade 3 or higher events in 35.8, 30.2 and 43.1 percent."],"whatItMeans":"The proof that a RAS inhibitor in colorectal cancer needs an EGFR antibody beside it, a principle that now shapes the trials of the pan-RAS and G12D inhibitors following behind.","caveats":["Progression-free survival was the primary endpoint; overall survival data were maturing.","KRAS G12C is 3 to 4 percent of metastatic colorectal cancer, so the trial is small by design.","The standard-care arm was trifluridine-tipiracil or regorafenib, both of which have modest activity."],"changedPractice":true,"participants":160},"route":"/key-papers/paper-fakih-codebreak-300-sotorasib-panitumumab-nejm-2023/","neighbours":{"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"},{"id":"kras-roadmap","kind":"roadmap","name":"KRAS roadmap: undruggable → G12C → pan-RAS","route":"/roadmaps/kras-roadmap/"}],"paper":[{"id":"paper-ostrem-kras-g12c-nature-2013","kind":"paper","name":"Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable","route":"/key-papers/paper-ostrem-kras-g12c-nature-2013/"},{"id":"paper-douillard-prime-panitumumab-ras-nejm-2013","kind":"paper","name":"Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME)","route":"/key-papers/paper-douillard-prime-panitumumab-ras-nejm-2013/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"kras-g12c-colorectal","kind":"cancer","name":"KRAS G12C-mutant colorectal cancer","route":"/cancers/kras-g12c-colorectal/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","route":"/technologies/kras-inhibitors/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"drug":[{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"},{"id":"regorafenib","kind":"drug","name":"Regorafenib","route":"/drugs/regorafenib/"},{"id":"sotorasib","kind":"drug","name":"Sotorasib","route":"/drugs/sotorasib/"},{"id":"trifluridine-tipiracil","kind":"drug","name":"Trifluridine/tipiracil","route":"/drugs/trifluridine-tipiracil/"}],"company":[{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"trial":[{"id":"codebreak-300","kind":"trial","name":"CodeBreaK 300","route":"/trials/codebreak-300/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}