Michelina Cairo, MD from Texas Oncology speaks about ESMO 2021 Abstract LBA1 - Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): Results of the randomized phase III DESTINY-Breast03 study (Enhertu).
Link to Abstract:
LBA1 Abstract -
Based on the outcomes of DESTINY-Breast01, T-DXd is a HER2-targeting antibody-drug conjugate that has been authorized for patients with advanced HER2+ mBC (NCT03248492). DESTINY-Breast03 (NCT03529110) is a multicenter, open-label, randomized phase 3 trial evaluating the effectiveness and safety of T-DXd against T-DM1 in patients with HER2+ mBC who had previously had trastuzumab and taxane treatment. This is the first randomized study of T-DXd in British Columbia.
The points were distributed in a 1:1 ratio. By blinded independent central review, the main outcome was progression-free survival (PFS) (BICR). Overall survival (OS), objective response rate (ORR), duration of response, PFS by the investigator, and safety are secondary goals.
524 points had been randomized as of May 21, 2021. The average age was 54 years old (range, 20-83). PFS had a hazard ratio of 0.2840 (P = 7.8 x 10-22); median PFS for T-DXd was not attained vs. 6.8 mo for T-DM1. T-DXd had an estimated 12-month OS event rate of 94.1 percent (95 percent CI, 90.3-96.4) and T-DM1 had an estimated 12-month OS event rate of 85.9 percent (95 percent CI, 80.9-89.7); HR: 0.5546 (95 percent CI, 0.3587-0.8576; P = 0.007172 did not exceed pre-specified significance limit). T-DXd had a median treatment length of 14.3 months (range: 0.7-29.8) vs. T-DM1 had a median treatment duration of 6.9 months (range: 0.7-25.1), with the identical incidence of TEAEs. There were no drug-related fatalities in either arm. Drug-related interstitial lung disease (ILD) was diagnosed in 10.5 percent of T-DXd patients (majority [9.7%] grade 1/2; 0 grade 4/5) vs 1.9 percent of T-DM1 patients (all grade 1/2).
In patients previously treated with trastuzumab and taxane for HER2+ mBC, T-DXd showed a statistically significant and clinically relevant increase in PFS compared to T-DM1. These findings show that T-DXd is tolerated, with manageable toxicity and a significantly improved ILD profile as compared to trials in severely pretreated patients. This research will lead to a change in the way HER2+ mBC is treated.
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