Dr Raghav on Trastuzumab Deruxtecan in HER2+ mCRC

Kanwal P. S. Raghav, MBBS, MD, associate professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, medical director, Division of Ambulatory Treatment Centers, The University of Texas MD Anderson Cancer Center, discusses primary findings from the phase 2 DESTINY-CRC02 trial (NCT04744831) of fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with metastatic colorectal cancer with HER2 amplification or overexpression.

DESTINY-CRC02 enrolled patients with unresectable or recurrent HER2-positive, BRAF wild-type, RAS wild-type or mutant mCRC. In stage 1 of this trial, patients were randomly assigned 1:1 to receive intravenous (IV) trastuzumab deruxtecan at either 5.4 mg/kg or 6.4 mg/kg every 3 weeks. In stage 2, an additional 42 patients were enrolled and received IV trastuzumab deruxtecan at 5.4 mg/kg every 3 weeks. The primary end point was confirmed overall response rate (cORR) by blinded independent central review. Key secondary end points included investigator-assessed cORR, duration of response (DOR), disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety.

In all patients who received trastuzumab deruxtecan at 5.4 mg/kg (n = 82), the cORR was 37.8%, all of which were partial responses (PRs). In the patients who received the agent at 6.4 mg/kg (n = 40), the cORR was 27.5%, all of which were PRs. These cORRs indicate the efficacy of this treatment at both dose levels, Raghav says.

The median DOR was 5.5 months at both dose levels, and the confirmed DCRs were 86.6% and 85.0% at 5.4 mg/kg and 6.4 mg/kg, respectively. The median PFS was 5.8 months at 5.4 mg/kg and 5.5 months at 6.4 mg/kg. The median OS was 13.4 months at 5.4 mg/kg and not evaluable at 6.4 mg/kg. In patients with a HER2 immunohistochemistry (IHC) of 3+ (n = 64) and a HER2 IHC of 2+/ISH+ (n = 18), the ORRs achieved with the agent were 46.9% and 5.6%, respectively. In patients with RAS wild-type (n = 68) and RAS-mutant (n = 14) disease, the ORRs were 39.7% and 28.6%, respectively.

The overall safety profile favored the 5.4-mg/kg dose level, Raghav explains. Treatment-emergent adverse effects (TEAEs) occurred in 98.8% of patients who received trastuzumab deruxtecan at 5.4 mg/kg and 100% of those who received the agent at 6/4 mg/kg. Drug-related TEAEs occurred in 91.6% and 94.9% of patients at 5.4 mg/kg and 6.4 mg/kg, respectively.

Disclosures: Dr Raghav reports honoraria from Bayer, Daiichi Sankyo/Astra Zeneca, Eisai, Merck, and Seagen; consulting or advisory roles with Bayer, Daiichi Sankyo/Astra Zeneca, Eisai, Merck, and Seagen; and research funding from AbbVie (Inst), Bayer (Inst), Daiichi Sankyo/Astra Zeneca (Inst), Eisai (Inst), Guardant Health (Inst), HiberCell (Inst), Innovent Biologics (Inst), Janssen (Inst), Merck Serono (Inst), Roche/Genentech (Inst), UCB (Inst), and Xencor (Inst).