Trastuzumab deruxtecan shows activity in HER2+ metastatic colorectal cancer

The DESTINY-CRC01 trial was one of the first studies to show that the targeted therapy trastuzumab deruxtecan (T-DXd) was able to produce a meaningful response rate among HER2-positive metastatic colorectal cancer (mCRC) patients. Research from the DESTINY-CRC02 trial was presented at the ASCO Annual Meeting 2023, demonstrating that T-DXd had equivalent anti-tumour activity at a lower dose in patients with HER2-positive mCRC.

HER2+ mCRC is a rare subset of colorectal cancer patients occurring in 2-3% of all patients with colorectal cancer. HER2 positive mCRC does not respond well to other important colorectal cancer therapies such as the anti-EGFR drugs cetuximab or panitumumab.

T-DXd is a combined therapy of an anti-HER2 targeted therapy (trastuzumab) linked to a deruxtecan, a potent topoisomerase I inhibitor which interferes with cancer cells’ ability to replicate, leading to their death.

The phase 2 DESTINY-CRC02 study included patients with RAS wildtype or mutant, HER2 overexpressing mCRC. The study aimed to determine the efficacy and safety of T-DXd at two different doses to find out if a lower dose would be as effective with a better risk-benefit profile. The clinical benefit of this targeted therapy was found to be similar at both doses (5.4 mg/kg, and 6.4 mg/kg). The safety analysis of the drug showed less toxicity at the lower dose, particularly to the bone marrow, which is a primary concern with this therapy.

These findings add to the evidence to support T-DXd as a meaningful treatment option for patients with HER2-positive metastatic disease.