{"entity":{"id":"paper-siena-destiny-crc01-trastuzumab-deruxtecan-lancet-oncol-2021","kind":"paper","name":"Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01)","aka":[],"tldr":"An antibody carrying a chemotherapy payload shrank 45 percent of HER2-positive bowel cancers that had already failed two or more treatments, including tumours that had progressed on other HER2 drugs.","summary":"Siena, Di Bartolomeo, Raghav and colleagues recruited patients from 25 clinics and hospitals in Italy, Japan, Spain, the United Kingdom and the United States with centrally confirmed HER2-expressing metastatic colorectal cancer that had progressed on two or more previous regimens, RAS and BRAF V600E wild-type tumours and ECOG score 0 or 1; previous HER2-targeted therapy other than trastuzumab deruxtecan was permitted. Patients were enrolled into three cohorts by HER2 expression level and received 6.4 mg/kg trastuzumab deruxtecan intravenously every three weeks. The primary endpoint was confirmed objective response in cohort A by independent central review.\n\nBetween February 2018 and July 2019, 78 patients were enrolled: 53 in cohort A (HER2-positive), seven in cohort B and 18 in cohort C.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(21)00086-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33961795/"}],"tags":["colorectal-evidence"],"related":["paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023","paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016"],"cancers":["colorectal","her2-amplified-colorectal"],"sections":["adcs","targeted-therapy"],"technologies":["adc"],"targets":["her2"],"drugs":["trastuzumab-deruxtecan"],"companies":["daiichi-sankyo"],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-crc02"],"people":["salvatore-siena","yoshino-takayuki"],"bottlenecks":["b-rare-cancers","b-toxicity-qol"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00086-3","pmid":"33961795","authors":"Siena S, Di Bartolomeo M, Raghav K, et al.","paperType":"rct","findings":["Confirmed objective response in 24 of 53 (45.3 percent, 95 percent CI 31.6 to 59.6) in the HER2-positive cohort, after a median 27.1 weeks of follow-up.","Grade 3 or worse treatment-emergent events occurring in at least 10 percent: decreased neutrophil count 17 of 78 (22 percent) and anaemia 11 (14 percent).","Five patients (6 percent) had adjudicated interstitial lung disease or pneumonitis, including two grade 5 events, the only treatment-related deaths."],"whatItMeans":"The antibody-drug conjugate route into HER2-positive colorectal cancer, extended by DESTINY-CRC02 at a lower dose; interstitial lung disease is the class risk that defines how the drug is monitored.","caveats":["Single-arm phase 2 in 53 evaluable patients at the registration dose.","Two treatment-related deaths from interstitial lung disease at 6.4 mg/kg; DESTINY-CRC02 tested 5.4 mg/kg partly for this reason.","Cohorts B and C, with lower HER2 expression, showed little activity."],"changedPractice":true,"participants":78},"route":"/key-papers/paper-siena-destiny-crc01-trastuzumab-deruxtecan-lancet-oncol-2021/","neighbours":{"paper":[{"id":"paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016","kind":"paper","name":"Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES)","route":"/key-papers/paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016/"},{"id":"paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023","kind":"paper","name":"Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER)","route":"/key-papers/paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"her2-amplified-colorectal","kind":"cancer","name":"HER2-amplified colorectal cancer","route":"/cancers/her2-amplified-colorectal/"}],"section":[{"id":"adcs","kind":"section","name":"Antibody-Drug Conjugates","route":"/fronts/adcs/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"company":[{"id":"daiichi-sankyo","kind":"company","name":"Daiichi Sankyo","route":"/companies/daiichi-sankyo/"}],"trial":[{"id":"destiny-crc02","kind":"trial","name":"DESTINY-CRC02","route":"/trials/destiny-crc02/"}],"person":[{"id":"salvatore-siena","kind":"person","name":"Salvatore Siena","route":"/people/salvatore-siena/"},{"id":"yoshino-takayuki","kind":"person","name":"Takayuki Yoshino","route":"/people/yoshino-takayuki/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"lancet-oncology","kind":"journal","name":"The Lancet Oncology","route":"/journals/lancet-oncology/"}],"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/"}]}}