Trastuzumab Deruxtecan Deemed “Practice-Changing” for HER2-Low Metastatic Breast Cancer

Phase 3 results support trastuzumab deruxtecan (T-DXd) as a new standard of care for patients with HER2-low metastatic breast cancer, according to a presentation at the 2022 ASCO Annual Meeting.¹

In the DESTINY-Breast04 trial, T-DXd significantly improved progression-free survival (PFS) and overall survival (OS), compared with physician’s choice of therapy, in patients with HER2-low metastatic breast cancer, regardless of hormone receptor (HR) status.

T-DXd is the first HER2-targeted therapy to demonstrate statistically significant and clinically meaningful improvements in PFS and OS over physician’s choice therapy in this population, according to study author Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.

“These results establish HER2-low metastatic breast cancer as a targetable population of breast cancer, with trastuzumab deruxtecan as a new standard of care in this setting,” Dr Modi said. “We anticipate these results to be practice-changing.”

For this phase 3 trial (ClinicalTrials.gov Identifier: NCT03734029), Dr Modi and colleagues enrolled patients with HER2-low, unresectable and/or metastatic breast cancer who had received 1 or 2 prior lines of chemotherapy for metastatic disease.

Patients were randomly assigned to T-DXd (n=373) or physician’s choice of therapy (n=184), which included capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel.

At a median follow-up of 18.4 months, there was a significant improvement in PFS and OS with T-DXd in the overall cohort and among patients with HR-positive disease.

In the overall cohort, the median PFS was 9.9 months with T-DXd and 5.1 months with physician’s choice (hazard ratio [HR], 0.50; 95% CI, 0.40-0.63; P <.0001). In the HR-positive group, the median PFS was 10.1 months and 5.4 months, respectively (HR, 0.51; 95% CI, 0.40-0.64; P <.0001).

In the overall cohort, the median OS was 23.4 months with T-DXd and 16.8 months with physician’s choice (HR, 0.64; 95% CI, 0.49-0.84; P =.0010). In the HR-positive group, the median OS was 23.9 months and 17.5 months, respectively (HR, 0.64; 95% CI, 0.48-0.86; P =.0028).

Dr Modi and colleagues observed similar results in an exploratory analysis of HR-negative patients. In this group, the median PFS was 8.5 months with T-DXd and 2.9 months with physician’s choice (HR, 0.64; 95% CI, 0.24-0.89). The median OS was 18.2 months and 8.3 months, respectively (HR, 0.48; 95% CI, 0.24-0.95).

The safety results were consistent with the known safety profiles of the drugs studied, according to Dr Modi. The rate of grade 3 or higher treatment-emergent adverse events (TEAEs) was 53% with T-DXd and 67% with physician’s choice.

TEAEs associated with discontinuation occurred in 16% of patients in the T-DXd arm and 8% in the physician’s choice arm. TEAEs associated with death occurred in 4% and 3%, respectively.

Lung toxicity was more common with T-DXd than with physician’s choice therapy (12.1% and 0.6%, respectively).

Results from this study were also published in The New England Journal of Medicine.²

Disclosures: This research was sponsored by Daiichi Sankyo and AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

1. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study. Presented at ASCO 2022; June 3-7, 2022. Abstract LBA3.
2. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. Published online June 5, 2022. doi:10.1056/NEJMoa2203690

This article originally appeared on Cancer Therapy Advisor