Trastuzumab-deruxtecan showed promising activity in patients with HER2-expressing mCRC

In the phase 2, open-label DESTINY-CRC01 trial, treatment of patients with HER2-expressing metastatic colorectal cancer (mCRC) with trastuzumab-deruxtecan (T-DXd) showed promising activity and durability, as well as a manageable safety profile.

Of all patients with mCRC, less than 5% have a HER2-expressing tumour [1]. Currently, no approved HER2-targeted therapies exist for mCRC. T-DXd is an antibody-drug conjugate of a humanised anti-HER2 antibody bound to a topoisomerase I inhibitor by a cleavable linker. The previously published primary results of the DESTINY-CRC01 trial (NCT03384940) demonstrated anti-tumour activity of T-DXd in patients with HER2-expressing mCRC [2]. Dr Takayuki Yoshino (National Cancer Center Hospital East, Japan) presented updated results [3].

Enrolled were 86 patients with RAS wildtype mCRC that progressed in 2 or more prior regimens. Patients in cohort A (n=53) were HER2-positive (IHC3+ or IHC2+/ISH+), patients in Cohort B (n=15) were HER2-borderline (IHC2+/ISH-), and patients in Cohort C (n=18) were HER2-negative (IHC1+). Patients were treated with 6.4 mg/kg of T-DXd every 3 weeks. The primary endpoint was confirmed objective response rate in cohort A.

The objective response rate was 45.3% in Cohort A versus 0% in both Cohort B and Cohort C. Disease control rate was 83.0%, 60.0%, and 22.2% in the respective cohorts. The median duration of response in Cohort A was 7.0 months. Median progression-free and overall survival results are summarised in the Figure.

Figure: Progression-free and overall survival in DESTINY-CRC01 [3]



The safety profile was consistent with the known safety profile of T-DXd. An adverse event of special interest is interstitial lung disease, which occurred in 8 of 86 patients (4 patients grade 2, 1 patient grade 3, and 3 patients grade 5). These results are promising and support future trials with T-DXd in HER2-positive mCRC.

1. Siena S, et al. Ann Oncol. 2018;29:1108-1119.
2. Siena S, et al. Lancet Oncol. 2021:22:779-789.
3. Yoshino T, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): Final results from a phase 2, multicenter, open-label study (DESTINY-CRC01). Abstract 3505, ASCO 2021 Virtual Meeting, 4–8 June.

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Posted on 12 August 202117 May 2024