T-DXd Improves Survival vs T-DM1 in HER2+ Advanced Breast Cancer

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Trastuzumab deruxtecan (T-DXd) improves overall survival (OS), compared with trastuzumab emtansine (T-DM1), in patients with previously treated, HER2-positive, advanced breast cancer, according to updated results from the DESTINY-Breast03 trial.

The update also showed a continued benefit in progression-free survival (PFS) with T-DXd. These results further support the use of T-DXd as the second-line standard care in this patient population, according to researchers. 

The update was presented at the San Antonio Breast Cancer Symposium 2022 and simultaneously published in The Lancet.1,2


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The phase 3 DESTINY-Breast03 trial (ClinicalTrials.gov Identifier: NCT03529110) recruited patients with HER2-positive, unresectable or metastatic breast cancer who had previously received trastuzumab and a taxane in the metastatic, neoadjuvant, or adjuvant setting and had a recurrence within 6 months of treatment. 

A total of 524 patients were randomly assigned to receive T-DXd at 5.4 mg/kg (n=261) or T-DM1 at 3.6 mg/kg (n=263) every 3 weeks. The median age was 54.3 years in the T-DXd arm and 54.2 years in the T-DM1 arm. Nearly all patients were women (99.6% in both arms), most had visceral disease (70.5% in the T-DXd arm and 70.3% in the T-DM1 arm), roughly half were hormone receptor-positive (50.2% and 51.0%, respectively), and a minority had brain metastasis at baseline (16.5% and 14.8%, respectively).

The median follow-up was 28.4 months in the T-DXd arm and 26.5 months in the T-DM1 arm. The median treatment duration was 18.2 months and 6.9 months, respectively.

At the data cutoff, 29.2% of patients in the T-DXd arm remained on treatment, as did 6.9% of patients in the T-DM1 arm. The primary reason for discontinuation was disease progression (36.6% and 68.2%, respectively).

Although the median OS was not reached in either treatment arm, T-DXd was associated with significantly improved OS compared with T-DM1 (hazard ratio [HR], 0.64; 95% CI, 0.47-0.87; P =.0037). The OS rates were higher in the T-DXd arm than in the T-DM1 arm at 12 months (94.1% and 86.0%, respectively) and 24 months (77.4% and 69.9%, respectively). 

The median PFS was 28.8 months in the T-DXd arm and 6.8 months in the T-DM1 arm (HR, 0.33; 95% CI, 0.26-0.43; P <.000001). PFS rates were higher in the T-DXd arm than in the T-DM1 arm at 12 months (75.2% and 33.9%, respectively) and 24 months (53.7% and 26.4%, respectively).

Treatment-related adverse events (AEs) occurred in 98.1% of patients in the T-DXd arm and 87.4% of those in the T-DM1 arm. Grade 3 or higher treatment-related AEs occurred in 47.1% and 42.1%, respectively.

The most common AEs with T-DXd were nausea (77.0%) and vomiting (51.8%). The most common AEs with T-DM1 were decreased platelet count (43.7%) and aspartate aminotransferase increase (41.4%). Interstitial lung disease/pneumonitis occurred in 15.2% of patients in the T-DXd arm and 3.1% of patients in the T-DM1 arm.

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

References

1 .Hurvitz SA, Hegg R, Chung W-P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results of the randomized, phase 3 study DESTINY-Breast03. Presented at SABCS 2022. December 6-10, 2022. Abstract GS2-02.
2. Hurvitz SA, Hegg R, Chung W-P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. Published online December 7, 2022. doi:https://doi.org/10.1016/S0140-6736(22)02420-5



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