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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Monday, December 19, 2022
The phase III findings from the DESTINY-Breast03 trial favored fam-trastuzumab deruxtecan-nxki (T-DXd) over standard-of-care trastuzumab emtansine (T-DM1)—HER2-targeting antibody-drug conjugates—in patients with HER2-positive metastatic breast cancer, according to Sara Hurvitz, MD, FACP, of the University of California, Los Angeles, and colleagues. With further follow-up, results from the prespecified overall survival analysis were reported during the 2022 San Antonio Breast Cancer Symposium (SABCS; Abstract GS2-02).
“The results of this analysis demonstrated remarkable overall survival and continued progression-free survival benefit with T-DXd, further supporting the use of T-DXd over T-DM1 in the second-line setting,” commented Dr. Hurvitz in a press release from the American Association for Cancer Research. “We can confirm that the previously demonstrated benefit from T-DXd in progression-free survival improvement transforms into a statistically significant improvement in overall survival.”
Patients who were previously treated with trastuzumab and taxane were randomly assigned to receive either T-DXd (n = 261) or T-DM1 (n = 263). The risk of death was reduced by 36% with T-DXd (P = .0037). In both arms, the median duration of overall survival was not reached. The landmark 12-month overall survival rate was higher with T-DXd than with T-DM1 (94.1% vs. 86.0%); the 24-month overall survival rates were 77.4% and 69.9%, respectively. According to the investigators, the P value for overall survival crossed the prespecified boundary (P = .013) and was statistically significant. The median duration of progression-free survival by blinded independent central review was 28.8 months with T-DXd and 6.8 months with T-DM1 (nominal P < .000001).
Treatment-emergent adverse events of grade 3 or higher were observed in 56.4% of patients treated with T-DXd and in 51.7% of those who received T-DM1. Drug-related interstitial lung disease or pneumonitis, as evaluated by an independent adjudication committee, occurred at a higher rate with T-DXd than with T-DM1 (15.2% vs. 3.1%); adjudicated drug-related events of grade 4 or 5 were not reported with T-DXd.
Disclosure: For full disclosures of the study authors, visit sabcs.org.
2022 San Antonio Breast Cancer Symposium
