{"entity":{"id":"colorectal-failed-programmes","kind":"term","name":"Colorectal cancer: the failed and stopped programmes, and why","aka":["Negative trials in colorectal cancer"],"tldr":"The list of treatments that looked right and did not work: EGFR antibodies after surgery, heated chemotherapy washes of the abdomen, immunotherapy in ordinary bowel cancer, and treating a positive blood test before a scan shows anything.","summary":"Adjuvant EGFR antibodies failed twice in KRAS wild-type stage III colon cancer, in N0147 (three-year disease-free survival 71.5 with cetuximab against 74.6 percent without) and PETACC-8 (hazard ratio 1.05), and in the curative liver-metastasis setting New EPOC found active harm: median overall survival 55.4 months with cetuximab against 81.0 months without, a difference no one has explained. Intraperitoneal chemotherapy failed three times: PRODIGE 7 found no survival gain from adding oxaliplatin HIPEC to complete cytoreductive surgery (41.7 against 41.2 months) with more late complications, COLOPEC found no benefit from adjuvant HIPEC in T4 or perforated colon cancer, and PROPHYLOCHIP found none from systematic second-look surgery with HIPEC. Checkpoint inhibition in microsatellite-stable disease failed in IMblaze370, where atezolizumab with cobimetinib matched regorafenib exactly (hazard ratio 1.00). Circulating tumour DNA has so far failed as a treatment trigger rather than as a prognostic test: ALTAIR gave trifluridine/tipiracil to patients who turned ctDNA-positive after standard treatment and missed its disease-free survival endpoint (9.30 against 5.55 months, hazard ratio 0.79, p=0.107) while causing grade 3 or higher haematological toxicity in 73 percent, and DYNAMIC-III could not show that de-escalation in ctDNA-negative stage III disease is non-inferior, nor that escalation in ctDNA-positive disease helps. In access rather than efficacy, NICE did not recommend ziv-aflibercept (TA307, 2014) despite a positive phase 3 trial. The pattern is consistent: what works in bulky metastatic disease does not transfer to microscopic disease, and adding a drug to a curative pathway can cost lives.","asOf":"2026-09-24","links":[{"label":"NICE TA307: aflibercept for metastatic colorectal cancer (not recommended)","url":"https://www.nice.org.uk/guidance/ta307"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd","ctdna","msi"],"trials":["n0147","petacc-8","new-epoc","prodige-7","colopec","prophylochip","imblaze370","altair","dynamic-iii","velour"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},"route":"/terms/colorectal-failed-programmes/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"}],"trial":[{"id":"n0147","kind":"trial","name":"Alliance N0147","route":"/trials/n0147/"},{"id":"altair","kind":"trial","name":"ALTAIR","route":"/trials/altair/"},{"id":"colopec","kind":"trial","name":"COLOPEC","route":"/trials/colopec/"},{"id":"dynamic-iii","kind":"trial","name":"DYNAMIC-III","route":"/trials/dynamic-iii/"},{"id":"imblaze370","kind":"trial","name":"IMblaze370","route":"/trials/imblaze370/"},{"id":"new-epoc","kind":"trial","name":"New EPOC","route":"/trials/new-epoc/"},{"id":"petacc-8","kind":"trial","name":"PETACC-8","route":"/trials/petacc-8/"},{"id":"prodige-7","kind":"trial","name":"PRODIGE 7","route":"/trials/prodige-7/"},{"id":"prophylochip","kind":"trial","name":"PROPHYLOCHIP-PRODIGE 15","route":"/trials/prophylochip/"},{"id":"velour","kind":"trial","name":"VELOUR","route":"/trials/velour/"}]}}