# Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01)

Source: https://onco.cc/key-papers/paper-siena-destiny-crc01-trastuzumab-deruxtecan-lancet-oncol-2021/  
OnCo record `paper-siena-destiny-crc01-trastuzumab-deruxtecan-lancet-oncol-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Between February 2018 and July 2019, 78 patients were enrolled: 53 in cohort A (HER2-positive), seven in cohort B and 18 in cohort C.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: The Lancet Oncology
- Year: 2021
- DOI: 10.1016/S1470-2045(21)00086-3
- Authors: Siena S, Di Bartolomeo M, Raghav K, et al.
- 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.
- What it means: 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.

## Sources

- Lancet Oncol 2021: https://doi.org/10.1016/S1470-2045(21)00086-3
- PubMed: https://pubmed.ncbi.nlm.nih.gov/33961795/

## Connected records

- key papers: [Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES)](https://onco.cc/key-papers/paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016/), [Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER)](https://onco.cc/key-papers/paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [HER2-amplified colorectal cancer](https://onco.cc/cancers/her2-amplified-colorectal/)
- fronts: [Antibody-Drug Conjugates](https://onco.cc/fronts/adcs/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- targets: [HER2](https://onco.cc/targets/her2/)
- drugs: [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- companies: [Daiichi Sankyo](https://onco.cc/companies/daiichi-sankyo/)
- trials: [DESTINY-CRC02](https://onco.cc/trials/destiny-crc02/)
- people: [Salvatore Siena](https://onco.cc/people/salvatore-siena/), [Takayuki Yoshino](https://onco.cc/people/yoshino-takayuki/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)
- roadmaps: [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](https://onco.cc/roadmaps/colorectal-roadmap/)

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