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DESTINY-CRC01: Maintained efficacy of T-DXd in mCRC

Presented by
Dr Takayuki Yoshino, National Cancer Center Hospital East, Japan
ASCO GI 2022
Phase 2, DESTINY-CRC01
Trastuzumab deruxtecan (T-DXd) demonstrated encouraging activity and durable responses in patients with HER2-positive metastatic colorectal cancer (mCRC) in the phase 2 DESTINY-CRC01 study. Moreover, the final results of this study showed that the safety profile of T-DXd is acceptable. These results support further exploration of this agent in patients with HER2-positive mCRC [1].

The open-label, multicentre, phase 2 DESTINY-CRC01 study (NCT03384940) investigated the safety and efficacy of T-DXd in patients with mCRC across 3 cohorts. Cohort A included patients with true HER2-positive status (IHC 3+ or IHC 2+/ISH+; n=53). Cohort B (IHC 2+/IHC-; n=15) and cohort C (IHC 1+; n=18) included patients with less HER2 expression. The patients received doses of 6.4 mg/kg T-DXd, administered every 3 weeks. The primary analysis of this trial showed promising anti-tumour activity in cohort A and an acceptable safety profile of T-DXd in this population. After an additional 35 weeks of follow-up, Dr Takayuki Yoshino (National Cancer Center Hospital East, Japan) presented the final results of this trial.

After a median follow-up of 62.4 weeks in cohort A, the confirmed overall response rate was 45.3%. All of these responses were partial responses. There were no confirmed responses observed in cohorts B and C. The median duration of response was 7.0 months. Furthermore, the median progression-free survival was 6.9 months in cohort A, compared with 2.1 and 1.4 months in cohorts B and C, respectively. The median overall survival was 15.5 months in cohort A, demonstrating a clinically meaningful improvement over cohorts B and C (7.3 and 7.7 months). Notably, within cohort A, patients with IHC3+ status were significantly more likely to show a response than patients with IHC2+/ISH+ status.

The safety profile was consistent with the known safety profile of T-DXd. Approximately 65% of the patients experienced a grade 3 or higher treatment-emergent adverse event (TEAE). In 15.1% of the patients, a TEAE led to drug discontinuation. In addition, in 17.4% of the patients, dose reductions were incited by TEAEs. Interstitial lung disease (ILD)/pneumonitis occurred in 9.3% of the patients, with 4 grade 2 events, 1 grade 3 event, and 3 grade 5 events. The median time to adjudicated onset of ILD/pneumonitis was 61 days. Dr Yoshino argued that the safety profile of T-DXd is acceptable in this population but that ILD/pneumonitis remains an important risk that requires careful monitoring.

  1. 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 119, ASCO GI 2022, 20–22 January.


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