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• W4377012682 abstract "Sara A Hurvitz and colleagues reported updated results from DESTINY-Breast03, a randomised phase 3 trial comparing trastuzumab deruxtecan to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane.1Hurvitz SA Hegg R Chung WP 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. 2023; 401: 105-117Summary Full Text Full Text PDF PubMed Scopus (41) Google Scholar Previously, in DESTINY-Breast01, trastuzumab deruxtecan showed efficacy as third-line HER2-based treatment after trastuzumab emtansine, which led to accelerated approval in December, 2019.2Modi S Saura C Yamashita T et al.Trastuzumab deruxtecan in previously treated HER2-positive breast cancer.N Engl J Med. 2020; 382: 610-621Crossref PubMed Scopus (898) Google Scholar These results were consolidated in DESTINY-Breast02, in which the trastuzumab deruxtecan group had better overall survival than the investigator's choice group (trastuzumab plus capecitabine or lapatinib plus capecitabine).3Krop I, Park YH, Kim S-B, et al. Trastuzumab deruxtecan vs physician's choice in patients with HER2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: primary results of the randomized phase 3 study DESTINY-Breast02. San Antonio Breast Cancer Symposium; December 6–10, 2022 (abstr GS2-01).Google Scholar Now, in the updated findings from DESTINY-Breast03, trastuzumab deruxtecan was associated with improvement in progression-free survival compared with trastuzumab emtansine, but also in overall survival (hazard ratio 0·64, 95% CI 0·47–0·87; p=0·0037; 24-month overall survival: 77·4% vs 69·9%).1Hurvitz SA Hegg R Chung WP 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. 2023; 401: 105-117Summary Full Text Full Text PDF PubMed Scopus (41) Google Scholar The authors conclude that the overall survival data reaffirm trastuzumab deruxtecan as the standard of care in the second-line setting. However, a proof that overall survival is better when trastuzumab deruxtecan is introduced as second line requires that those patients in the conventional group have easy access to trastuzumab deruxtecan at progression, ideally offered by the sponsors to avoid variations due to availability or cost. Of the 182 patients who discontinued trastuzumab deruxtecan, 64 (35%) received trastuzumab emtansine. Conversely, only 42 (17%) of 243 patients discontinuing trastuzumab emtansine could receive third-line trastuzumab deruxtecan. The optimal sequencing is thus still not definitely defined. When selecting a second-line treatment for a patient, clinicians need to consider the major benefit in progression-free survival with trastuzumab deruxtecan, but also the risk of lung toxicity and other adverse events, quality of life, and costs.4Abuhelwa Z Alloghbi A Alqahtani A Nagasaka M Trastuzumab deruxtecan-induced interstitial lung disease/pneumonitis in ERBB2-positive advanced solid malignancies: a systematic review.Drugs. 2022; 82: 979-987Crossref PubMed Scopus (13) Google Scholar, 5Zhu Y Liu K Wang M Wang K Zhu H Trastuzumab deruxtecan versus trastuzumab emtansine for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: a cost-effectiveness analysis.Breast. 2022; 66: 191-198Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar I declare no competing interests. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trialTrastuzumab deruxtecan showed a significant improvement in overall survival versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer, as well as the longest reported median progression-free survival, reaffirming trastuzumab deruxtecan as the standard of care in the second-line setting. A manageable safety profile of trastuzumab deruxtecan was confirmed with longer treatment duration. Full-Text PDF Open AccessDESTINY-Breast03 trial: some questions remain – Authors' replyElif Hindié noted that the optimal treatment sequencing of trastuzumab deruxtecan is still not defined. We agree that the optimal treatment sequence of trastuzumab deruxtecan after disease progression and the outcomes of post-trial therapies are important to investigate. DESTINY-Breast03 was a global trial with participation from 15 different countries. Although data were collected on the post-trial anticancer therapies received, treatment crossover was not formally planned in the study and it was not designed to address sequencing. Full-Text PDF" @default.
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• W4377012682 title "DESTINY-Breast03 trial: some questions remain" @default.
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