乌鸦传媒

A presented at the virtual San Antonio Breast Cancer Symposium, found consistent outcome benefits for women with HER2-positive metastatic breast cancer treated with the HER2-targeting antibody-drug conjugate trastuzumab deruxtecan (T-DXd, Enhertu) versus the current standard of care with trastuzumab emtansine (T-DM1, Kadcyla) in second-line treatment.

In this exclusive 乌鸦传媒 video, first author , of the David Geffen School of Medicine at the University of California Los Angeles, discusses the results and her takeaways from the new data.

Following is a transcript of her remarks:

Hi, I'm Dr. Sarah Hurvitz from the University of California Los Angeles David Geffen School of Medicine, and I'm going to be talking about the DESTINY-Breast 03 phase III clinical trial comparing T-DXd to T-DM1.

At San Antonio, we presented the subgroup analysis from this trial. This is a large phase III study, the first phase III trial to be reported that evaluated T-DXd. And in this study, patients who had previously been treated with trastuzumab and a taxane for HER2-positive metastatic breast cancer were eligible to enroll and were randomly assigned one to one to T-DXd or T-DM1. T-DM1, of course, being the standard of care at the time this study was enrolling for second-line treatment.

At ESMO it was presented that the medium progression free survival [PFS] was highly significantly improved with T-DXd with a hazard ratio of 0.28, compared to T-DM1. The median PFS with T-DM1 was 6.8 months and was not reached with T-DXd.

At San Antonio, we looked at a number of subgroups to evaluate whether T-DXd was benefiting certain patient subgroups more or less. And actually when we looked based on hormone receptor status, prior pertuzumab [Perjeta] treatment (which was received by about 60% of the patients), presence or absence of visceral disease (most of the patients did have visceral disease), prior lines of therapy or patients with brain metastases, T-DXd benefited all of these subgroups that we looked at.

We also looked at the objective response rates based on these various subgroups and for all of these subgroups the ORR [objective response rate] was better with T-DXd. For most subgroups in excess of 70% objective response rate with T-DXd versus somewhere around 30% or so with T-DM1.

We then did a deep dive into the 82 patients who had brain metastases at baseline, and we looked at their outcomes. Patients were allowed on if they had stable brain metastases at baseline and were at least 2 weeks from radiation therapy, having recovered from its toxic effects. And interestingly saw that not only the medium PFS was better with T-DXd for patients with or without brain metastases, but also when we looked at the intracranial objective response rate by blinded independent central review, T-DXd was associated with an objective response rate in the brain of over 63%. And when you look at T-DM1, it was around 33% or so intracranial objective response rate.

So this is challenging our paradigm thinking that ADCs [antibody-drug conjugates] can't cross the blood brain barrier. Very interesting to see such a robust response in the brain, and this certainly deserves further interrogation in a prospective clinical trial.

The adverse events were similar to what was reported at ESMO. And interestingly, interstitial lung disease [ILD] did not vary based on whether patients came from Asia or non-Asian subgroups. The overall ILD rate was 10.5% with no grade four or five events.

So in summary, these data continue to support the use of T-DXd after trastuzumab and taxane in metastatic HER2-positive breast cancer for patients in the second-line setting or beyond. And I'm looking forward to seeing further studies like , and other trials -- for example, which will further evaluate the activity of T-DXd and those patients with active brain metastases. Thank you.

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