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Long-Term Survival Outcomes With Trastuzumab Deruxtecan vs Trastuzumab Emtansine in Patients With HER2-Positive Metastatic Breast Cancer
abstract
This abstract is available on the publisher's site.
Access this abstract nowTrastuzumab deruxtecan (T-DXd) demonstrated significantly improved efficacy over trastuzumab emtansine (T-DM1) in DESTINY-Breast03 (median follow-up, 28 months). We report updated efficacy and safety analyses, including secondary and exploratory efficacy endpoints (median follow-up, 41 months) of DESTINY-Breast03. Patients with advanced HER2-positive metastatic breast cancer previously treated with taxane and trastuzumab were randomized to T-DXd (5.4 mg per kg (261 patients)) or T-DM1 (3.6 mg per kg (263 patients)). The primary endpoint was progression-free survival (PFS) by blinded independent central review and was previously reported. The key secondary endpoint was overall survival (OS). Other secondary endpoints included objective response rate, duration of response and PFS (all by investigator assessment) and safety. At data cutoff, 20 November 2023, median PFS by investigator assessment was 29.0 versus 7.2 months (hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.24-0.38), the 36-month PFS rate was 45.7% versus 12.4% and median OS was 52.6 versus 42.7 months (HR, 0.73; 95% CI, 0.56-0.94) with T-DXd versus T-DM1, respectively. Treatment-emergent adverse events were consistent with the previous analyses. No new instances of grade ≥3 interstitial lung disease or pneumonitis occurred (all grade rate, 16.7% (T-DXd) versus 3.4% (T-DM1)). With longer follow-up, T-DXd continued to demonstrate superior efficacy over T-DM1 with a manageable safety profile. ClinicalTrials.gov registration: NCT03529110.
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Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial
Nat. Med. 2024 Jun 02;[EPub Ahead of Print], J Cortés, SA Hurvitz, SA Im, H Iwata, G Curigliano, SB Kim, JWY Chiu, JL Pedrini, W Li, K Yonemori, G Bianchini, S Loi, GS Borges, X Wang, T Bachelot, S Nakatani, S Ashfaque, Z Liang, A Egorov, E HamiltonFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Long-term survival analysis of the DESTINY-Breast03 trial — from study results to a practical perspective
DESTINY-Breast03 is a randomized phase III trial that tested trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2-positive advanced breast cancer after prior treatment with trastuzumab and taxanes.
Cortes et al reported the results of the long-term survival analysis of DESTINY-Breast03. With a median follow-up of 41.0 months, treatment with T-DXd confirmed a significant and clinically relevant improvement in progression-free survival, which was approximately four times longer with T-DXd than that with T-DM1 (median, 29.0 vs 7.2 months; HR, 0.30; 95% CI, 0.24–0.38). T-DXd was also associated with an improvement in overall survival of approximately 10.0 months (median, 52.6 vs 42.7 months; HR, 0.73; 95% CI, 0.56–0.94). The safety profile of T-DXd was consistent with the one observed in previous analyses, and no cumulative toxicities were observed with a longer follow-up.
These results confirm the role of T-DXd as the standard of care in the second-line setting for patients with HER2-positive breast cancer who progressed on a first-line treatment based on trastuzumab and taxanes.
Of note, approximately one-third of patients in the T-DM1 arm subsequently received T-DXd in the post-trial setting. The efficacy of T-DXd after progression on T-DM1 has already been demonstrated in the DESTINY-Breast02 trial1; nevertheless, these findings seem to support a potential higher benefit of T-DXd when used in earlier treatment settings.
Interstitial lung disease remains an important risk for patients treated with T-DXd. Patient monitoring and early management of pneumonitis/interstitial lung disease as soon as symptoms occur remain crucial.
The ongoing DESTINY-Breast09 (NCT04784715) trial is testing T-DXd with or without pertuzumab in the first-line setting for patients with HER2-positive breast cancer; the results are expected in 2025.
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