SABCS 2022: Second-Line Trastuzumab Deruxtecan Improves Overall Survival in Patients With Metastatic Breast Cancer
Benefit for overall and progression-free survival maintained with longer treatment duration, along with a manageable safety profile
WEDNESDAY, Dec. 7, 2022 (HealthDay News) – Second-line treatment with trastuzumab deruxtecan (T-DXd) was associated with significantly longer overall survival in patients with HER2-positive metastatic breast cancer (mBC) versus trastuzumab emtansine (T-DM1), according to a study presented at the San Antonio Breast Cancer Symposium, held from Dec. 6 to 10.
Sara A. Hurvitz, M.D., from the University of California Los Angeles, and colleagues compared the efficacy and safety of T-DXd to T-DM1 in patients with HER2-positive metastatic breast cancer that progressed on or after first-line treatment as part of the DESTINY-Breast03 trial. While previously published interim results showed that patients treated with T-DXd had significantly longer progression-free survival, overall survival data had not been reached in the first interim analysis. This new analysis provided overall survival data, as well as updated progression-free survival and safety data.
A total of 524 patients with HER2-positive mBC, previously treated with trastuzumab and a taxane and showing progression within six months, were randomly assigned to either T-DXd (261 patients; 5.4 mg/kg every three weeks) or T-DM1 (263 patients; 3.6 mg/kg every three weeks).
During a median study follow-up of 28.4 months for the T-DXd arm and 26.5 months for the T-DM1 arm, the researchers found that the risk for death was 36 percent lower with T-DXd (P = 0.0037). The overall survival rate at 12 months was 94.1 percent for T-DXd versus 86.0 percent for T-DM1, and at 24 months, the corresponding overall survival rates were 77.4 and 69.9 percent. The prespecified boundary for overall survival was crossed (P = 0.013), but median overall survival was not reached.
“The fact that treatment with T-DXd was associated with not only a significant improvement in progression-free survival but also, more importantly, in overall survival makes T-DXd the gold standard therapy for HER2-positive metastatic breast cancer after treatment with a taxane and trastuzumab,” Hurvitz told Elsevier’s PracticeUpdate. “I would no longer view T-DM1 as a recommended second-line option in light of these significant survival benefits.”
In an updated analysis, median progression-free survival by blinded independent central review was 28.8 months with T-DXd versus 6.8 months with T-DM1 (hazard ratio, 0.33; P < 0.000001). Additionally, grade 3 or higher treatment-emergent adverse events were seen in 56.4 percent of T-DXd-treated patients and 51.7 percent of T-DM1-treated patients. An independent adjudication committee found drug-related interstitial lung disease/pneumonitis occurred in 39 patients (15.2 percent) in the T-DXd group and eight patients (3.1 percent) in the T-DM1 group. There were no adjudicated drug-related grade 4 or 5 adverse events seen with T-DXd.
“The efficacy and tolerability of T-DXd in the first-line setting is an outstanding question, given its marked activity in the second-line setting and beyond, and is being evaluated in the phase III DESTINY-Breast09 trial,” Hurvitz told Elsevier’s PracticeUpdate. “One question that remains unanswered is the efficacy of T-DM1 after progression on T-DXd. We are planning on studying outcomes of patients treated as standard of care with T-DM1 after T-DXd on Destiny-Breast03.”
Hurvitz disclosed financial ties to the pharmaceutical industry, including Daiichi Sankyo and AstraZeneca, which funded the study.
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