T-DXd Benefit May Extend to Earlier Settings and HER2-Low Breast Cancers

According to Aditya Bardia, MD, MPH, FASCO, the approval of trastuzumab deruxtecan-nxki (T-DXd; Enhertu) moves it into an earlier line of treatment, particularly one that does not require previous use of chemotherapy.¹ Previously, T-DXd was available only for patients with HER2-low metastatic breast cancer who have undergone at least 1 line of chemotherapy.²

Bardia, a professor in the department of Medicine in theDivision of Hematology/Oncology, a director of Translational Research Integration, and a member of Signal Transduction and Therapeutics at UCLA Health Jonsson Comprehensive Cancer Center, emphasized that this approval would also make T-DXd a viable treatment option for HER2-low and HER2-ultralow metastatic breast cancer. T-DXd, he reiterated, works on most patient subgroups, including patients with both high and low disease burden, as well as for patients with or without rapid disease progression following frontline therapy.

At the 2024 San Antonio Breast Cancer Symposium (SABCS), where Bardia spoke with CancerNetwork^®, he gave a presentation on the phase 3 DESTINY-Breast06 trial (NCT04494425), the data of which informed the FDA’s decision.³ For patients with a time-to-progression (TTP) of less than 6 months, the median progression-free-survival (PFS) with T-DXd was 14.0 months compared with the 6.5 months achieved with physician’s choice of treatment (TPC; HR, 0.38; 95% CI, 0.25-0.59). T-DXd yielded a median PFS of 13.2 months compared with 6.9 months with TPC for patients with a TTP between 6 and 12 months (HR, 0.69; 95% CI, 0.43-1.12). For patients who progressed after 12 months, median PFS with T-DXd was 12.9 months compared with 8.2 months with TPC (HR, 0.67; 95% CI, 0.51-0.88).

Also, T-DXd showed a clinically meaningful improvement for median PFS compared with TPC regardless of TTP on a first-line endocrine therapy and CDK4/6 inhibitors.

Transcript:

T-DXd is currently approved for HER2-low metastatic breast cancer in patients who’ve received at least 1 prior line of chemotherapy.With DESTINY-Breast06,if T-DXd is approved, that would move T-DXdto an earlier line [of treatment].You would not require prior use of chemotherapy before using T-DXd. Also, it would be for both HER2-low as well as HER2-ultralow [breast cancer], which refers to tumors with very low expression of HER2—lessthan 10% of cells expressing HER2. 

T-DXd works regardless of the [patient] subgroup, both in patients with high disease burdenand low disease burden, and in patients who have rapid disease progression on first-line therapy and those who do not. In pretty much all the subgroups, T-DXd works.

References

1. Enhertu approved in the US as first HER2-directed therapy for patients with HER2-low or HER2-ultralow metastatic breast cancer following disease progression after one or more endocrine therapies. News release. FDA. January 27, 2024. Accessed January 27, 2024. https://tinyurl.com/5n8ab8sk
2. FDA approves fam-trastuzumab deruxtecan-nxki for HER2-low breast cancer. News release. FDA. August 05, 2022. Accessed December 17, 2024. https://tinyurl.com/yc2vjam5
3. Bardia A, Hu X, Dent R, et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) by pace of disease progression on prior endocrine-based therapy: additional analysis from DESTINY-Breast06. Presented at: San Antonio Breast Cancer Conference; December 10-14, 2024; San Antonio, TX. Abstract LB1-04.