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T-DXd Shows 'Truly Remarkable' Activity in Advanced HER2-Positive Breast Cancer

— Updated data solidify ADC as standard-of-care second-line therapy, says Sara Hurvitz, MD

MedpageToday

Updated results presented at the recent San Antonio Breast Cancer Symposium (SABCS) demonstrated the continued superiority of the HER2-targeting antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd, Enhertu) versus the current standard of care with trastuzumab emtansine (T-DM1, Kadcyla) as second-line treatment.

In this exclusive 鶹ý video, , of the David Geffen School of Medicine at the University of California Los Angeles, discusses the team's updated data on DESTINY-Breast03.

Following is a transcript of her remarks:

The DESTINY-Breast03 clinical trial is a phase III randomized study comparing T-DXd to T-DM1 in patients with HER2 positive metastatic breast cancer that had previously been treated with trastuzumab emtansine.

Previously, we reported that the median progression-free survival was significantly improved with T-DXd compared to T-DM1 -- those results were reported in 2021. And what we reported at SABCS were the updated overall survival results, which are now more mature, as well as updated progression-free survival results.

With the updated overall survival results, we see that the median overall survival was not yet reached for either treatment arm. However, patients treated in the T-DXd arm had a 36% lower risk of death. That was highly statistically significant, meeting the key secondary endpoint of OS [overall survival] benefit. Moreover, the median progression-free survival with T-DXd was found to be 28.8 months; with T-DM1 it was 6.8 months, so median PFS with T-DXd was roughly four times longer than with T-DM1.

In addition, we see about 21% of patients treated with T-DXd able to achieve a complete response of their disease -- so truly remarkable results in terms of activity.

These updated results solidly placed T-DXd as the standard-of-care second-line therapy after trastuzumab emtansine in areas where T-DXd is available. It's also notable that while interstitial lung disease [ILD] was noted in about 15% of patients, which is a bit higher than we reported in 2021, that was owing to longer treatment duration and longer follow-up and due to more grade 1 and 2 events. But there were no additional grade 3 events and no grade 4 or 5 adjudicated drug-related ILD events, which is reassuring.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.