KEY TAKEAWAYS
- The DESTINY-Breast03 is a randomized, open-label, Phase 3 trial that evaluated the efficacy and safety of trastuzumab deruxtecan and trastuzumab emtansine in HER2-positive metastatic breast cancer patients.
- The primary endpoint was progression-free, and overall survival was the key secondary endpoint.
- A total of 524 patients were randomized to trastuzumab deruxtecan or trastuzumab emtansine.
- Results showed that trastuzumab deruxtecan significantly increased overall survival compared to trastuzumab emtansine (HR 0·64; 95% CI 0·47-0·87]; p=0·0037).
- Trastuzumab deruxtecan had a manageable safety profile with no grade 4 or 5 events.
The progression-free survival interim analysis of the DESTINY-Breast03 study revealed an improvement in progression-free survival between trastuzumab deruxtecan and trastuzumab emtansine among patients with HER2-positive metastatic breast cancer. DESTINY-objective Breast03 was to assess the efficacy and safety of trastuzumab deruxtecan and trastuzumab emtansine.
This phase 3 open-label, randomized, multicentre trial was conducted at 169 research centers in North America, Asia, Europe, Australia, and South America. Eligible patients were at least 18 years old, had HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab and a taxane, had an Eastern Cooperative Oncology Group performance status of 0-1, and at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomized (1:1) to receive either trastuzumab deruxtecan 5.4 mg/kg or trastuzumab emtansine 3.6 mg/kg, delivered intravenously every 3 weeks.
The randomization was stratified by hormone receptor status, prior therapy with pertuzumab, and history of visceral disease and maintained via an interactive web-based system. A balanced block randomization with a block size of 4 was utilized within each stratum. Both patients and researchers were aware of the administered therapy. The primary outcome was progression-free survival, as determined by a blinded, independent central review. The most important secondary goal was overall survival, and this prespecified second overall survival interim analysis provides updated results for overall survival, effectiveness, and safety. Utilizing the entire analysis set, efficacy analyses were done. All randomly assigned patients who received at least 1 dosage of the study therapy were included in the safety assessments.
Between July 20, 2018, and June 23, 2020, 699 individuals were screened for eligibility, and 524 were enrolled and randomly assigned to receive either trastuzumab deruxtecan (n=261) or trastuzumab emtansine (n=263). Trastuzumab deruxtecan had a median duration of follow-up of 28.4 months (IQR 22.1-32.9), whereas trastuzumab emtansine had a median duration of 26.5 months (14.5-31.3). Based on a blinded, independent central evaluation, the median progression-free survival for trastuzumab deruxtecan was 28.8 months (95% confidence interval [CI]: 22.4-37.9) versus 6.8 months (5.6-8.2) for trastuzumab emtansine (hazard ratio [HR]: 0.33 [95% CI: 0.26-0.43]; nominal p<0.0001).
Median overall survival was not reached (95% CI: 40.5 months-not estimable) with 72 (28%) general survival events in the trastuzumab deruxtecan group and was not compared (34.0 months-not estimable) with 97 (37%) overall survival events in the trastuzumab emtansine group (HR: 0.64; 95% CI: 0.47-0.87); p = 0.0037. About 145 (56%) versus 135 (52%) individuals receiving trastuzumab deruxtecan or trastuzumab emtansine experienced treatment-emergent adverse events of grade 3 or worse. No grade 4 or 5 occurrences were seen in any group.
Trastuzumab deruxtecan demonstrated a statistically significant improvement in overall survival compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer and the longest reported median progression-free survival, reaffirming its status as the standard of care in the second-line setting. Longer treatment duration validated the tolerable safety profile of trastuzumab deruxtecan.
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02420-5/fulltext
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03529110
Hurvitz S, Hegg R, Chung W, Im S, Jacot W, Ganju V, Chiu J, Xu B, Hamilton E, Madhusudan S, Iwata H, Altintas S, Henning J, Curigliano G, Perez-Garcia J, Kim S, Petry V, Huang C, Li W, Frenel J, Antolin S, Yeo W, Bianchini G, Loi S, Tsurutani J, Egorov A, Liu Y, Cathcart J, Ashfaque S, Cortés J. 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. 2023 Jan 14;401(10371):105-117. doi: 10.1016/S0140-6736(22)02420-5. Epub 2022 Dec 7. PMID: 36495879.
