Dr Raghav on the Rationale Behind DESTINY-CRC02 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 the rationale behind the phase 2 DESTINY-CRC02 trial (NCT04744831) evaluating fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with metastatic colorectal cancer (mCRC) with HER2 amplification or overexpression.

HER2 amplification or overexpression occurs in approximately 2% to 3% of patients with mCRC, Raghav begins, adding that HER2-positivity is enriched in the RAS/BRAF wild-type patient population and appears to be a negative predictive biomarker for the efficacy of anti-EGFR therapy.

Evidence has demonstrated that HER2-targeted therapies could provide efficacy in this subset of patients, and the phase 2 DESTINY-CRC01 trial (NCT03384940) previously showed that the trastuzumab deruxtecan generated activity in this patient population, eliciting an overall response rate (ORR) of 45.3%, Raghav adds.

Raghav says DESTINY-CRC02 aimed to answer 2 questions: whether a dose of 5.4 mg/kg would be as effective and have a better risk/benefit profile vs 6.4 mg/kg, and whether patients with RAS-mutant disease with HER2 amplification could benefit from HER2-targeted therapies.

Primary results from DESTINY-CRC02 presented at the 2023 ASCO Annual Meeting showed that the antibody-drug conjugate produced a confirmed ORR (cORR) of 37.8% (95% CI, 27.3%-49.2%) among patients treated with 5.4 mg/kg of trastuzumab deruxtecan (n = 82), compared with 27.5% (95% CI, 14.6%-43.9%) for those who received 6.4 mg/kg (n = 40). Patients with RAS-mutant mCRC treated with 5.4 mg/kg of trastuzumab deruxtecan (n = 14) experienced an ORR 28.6% (95% CI, 8.4%-58.1%).