# DESTINY-CRC01: trastuzumab deruxtecan in HER2-expressing metastatic colorectal cancer

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

## TL;DR

Trastuzumab deruxtecan shrank tumours in about 45 percent of patients with HER2-high colorectal cancer, including those who had already received other HER2 drugs, but did nothing for tumours with low HER2 expression and carried a risk of lung inflammation.

## Summary

Phase 2 study of 86 patients with HER2-expressing, RAS and BRAF wild-type metastatic colorectal cancer after at least two regimens, treated with trastuzumab deruxtecan 6.4 mg/kg in three cohorts by HER2 level.

In the HER2 immunohistochemistry 3+ or 2+ with amplification cohort, objective response was 45.3 percent with median progression-free survival 6.9 months, including responses after prior HER2 therapy; no responses were seen in the low-expression cohorts, and interstitial lung disease occurred in 9 percent with some deaths.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- 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: Objective response 45.3 percent in HER2-positive cohort A; median progression-free survival 6.9 months.; No responses in HER2 2+ non-amplified or 1+ cohorts; interstitial lung disease 9.3 percent.
- What it means: Trastuzumab deruxtecan is an option for HER2-positive colorectal cancer after HER2 antibodies, and it contributed to the tumour-agnostic approval for HER2 3+ solid tumours; lung monitoring is essential.
- Caveats: Single-arm; interstitial lung disease including fatal cases.; The 6.4 mg/kg dose is higher than that used in breast cancer.

## Sources

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

## Connected records

- cancers: [HER2-amplified colorectal cancer](https://onco.cc/cancers/her2-amplified-colorectal/)
- drugs: [CRC01](https://onco.cc/drugs/crc01/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

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