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SABCS 2022 | DESTINY-Breast02: high levels of efficacy of T-DXd in previously treated HER2+ breast cancer

Ian Krop, MD, PhD, Smilow Cancer Hospital, Yale New Haven, CT, provides an overview of the Phase III DESTINY-Breast-2 trial (NCT03523585) which evaluated trastuzumab deruxtecan (T-DXd) versus treatment of physicians choice in patients who were previously treated with rtastuzumab emtansine (T-DM1). This study demonstrated that T-DXd, when compared with capecitabine and lapatinib or capecitabine and trastuzumab, resulted in higher response rates and longer survival in the third line setting in previously treated patients woth HER2-positive metastatic breast cancer. This interview took place at the San Antonio Breast Cancer Symposium (SABCS) 2022 in San Antonio, TX.

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Transcript (edited for clarity)

The DESTINY-Breast02 trial was a study of trastuzumab deruxtecan which is a HER2 directed antibody-drug conjugate. And the study was looking at patients with HER2-positive metastatic breast cancer, who previously had T-DM1, and it was randomizing those patients to either trastuzumab deruxtecan or treatment of physicians’ choice. The reason to do this trial was because we had previously shown in the destiny of Breast01 trial that trastuzumab deruxtecan was very effective in patients who previously had T-DM1...

The DESTINY-Breast02 trial was a study of trastuzumab deruxtecan which is a HER2 directed antibody-drug conjugate. And the study was looking at patients with HER2-positive metastatic breast cancer, who previously had T-DM1, and it was randomizing those patients to either trastuzumab deruxtecan or treatment of physicians’ choice. The reason to do this trial was because we had previously shown in the destiny of Breast01 trial that trastuzumab deruxtecan was very effective in patients who previously had T-DM1. The median progression-free survival in that study was 19 months, and that led to the accelerated approval of T-Dxd in that setting. But that was a single arm Phase II trial, and so it needed validation in a larger trial. And so the reason to do DESTINY-Breast02 was to confirm the results of DESTINY-Breast01. So that was designed in that way looking at the same rough, similar population of post T-DM1, HER2 positive metastatic breast cancer.

What we found in this randomized trial that was reported at San Antonio this year was that T-DXd was markedly superior to treatment of physician choice, which in this case was capecitabine with trastuzumab or capecitabine with lapatinib. In terms of progression-free survival, so the hazard ratio is about 0.36, so a 64% reduction in the risk of progression or death. The median PFS was about 18 months with T-DXd, about 7 months with treatment of physician choice. So a pretty big difference. And because the PFS benefit was significant, we also looked at overall survival. And even at this relatively early analysis, overall-survival also significantly favored T-DXd over TPC. So there’s about a 13 month longer overall-survival with T-DXd compared to treatment of physician’s choice. So from those two key efficacy endpoints, T-DXd was clearly substantially better. You looked at things like response rate and clinical benefit rate. Those also highly favored T-DXd. So that was the main take home message in terms of efficacy.

In terms of safety, pretty much the same as what we’ve seen in prior T-DXd trials. The most common adverse events with T-DXd or nausea, vomiting, they tend to be low grade, but it does benefit patients to use prophylactic antiemetics. The serious potential adverse event, we know with T-DXd is interstitial lung disease or ILD. In our study, the rate of overall ILD was about 10%, which is similar to what we’ve seen in other T-DXd studies. They’re actually even a little lower. Most of those events were low grade, but unfortunately two patients or 0.5% of the population did have fatal ILD. What was that was felt to be related to T-DXd? So again, this just further highlights that we have to pay attention to this toxicity. We have to monitor patients when they’re on T-DXd.

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