Trastuzumab Deruxtecan Superior to T-DM1 in the Second-Line Setting for HER2-Positive Metastatic Breast Cancer

Trastuzumab Deruxtecan Superior to T-DM1 in the Second-Line Setting for HER2-Positive Metastatic Breast Cancer

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At the 2022 San Antonio Breast Cancer Symposium, Sara Hurvitz, MD, David Geffen School of Medicine – UCLA, Los Angeles, California, presented updated results from the phase 3 Destiny-Breast03 trial, comparing trastuzumab deruxtecan with trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer who progressed on first-line treatment. 

This analysis demonstrated a benefit in both overall and progression-free survivals from trastuzumab deruxtecan in this patient population when compared to T-D1M. Dr Hurvits concluded the data further supports the use of trastuzumab deruxtecan over T-DM1 in the second-line setting.

Transcript:

Hi. I'm Dr Sarah Hurvitz, professor of medicine at the David Geffen School of Medicine at UCLA Jonsson Comprehensive Cancer Center. Here at San Antonio, we presented the updated results of the DESTINY-Breast03 clinical trial. This was a phase three study comparing trastuzumab deruxtecan versus trastuzumab emtansine (T-DM1) in metastatic HER2 positive breast cancer patients who had received and had progression on trastuzumab and a taxane for their disease. The data was originally presented just over a year ago at ESMO 2021 when we presented median progression-free survival results for the patients, and showed a stunning improvement in progression-free survival associated with trastuzumab deruxtecan. At that time, the overall survival results were not mature. And so here at San Antonio, we presented the updated overall survival results, which had matured at the time of this reporting. There were 169 overall survival events at the time of data cutoff, and we set our P-value for significance at 0.013.

At our reporting, the median overall survival for both arms was not yet reached. However, there was a statistically significant improvement in overall survival associated with trastuzumab deruxtecan with a hazard ratio of 0.64. In addition, we updated the medium progression-free survival results associated with this drug, and showed that trastuzumab deruxtecan was associated with a median progression-free survival of 28.8 months compared to 6.8 months with T-DM1. This was 4 times better median progression-free survival with trastuzumab deruxtecan strongly in favor of using that agent in the second line setting and beyond. The objective response rate for trastuzumab deruxtecan was almost 80%, with 21% of patients having a complete response. Again, these numbers are better than seen with T-DM1, significantly better.

Safety was also evaluated and with longer follow up and longer treatment duration with trastuzumab deruxtecan. We're seeing similar rates of adverse events all grade. We do have to watch for nausea and vomiting with trastuzumab deruxtecan and proactively treat patients to prevent and treat that. And we also see higher rates of alopecia with trastuzumab deruxtecan. In terms of serious side effects or grade 3-4 adverse events, the rates were fairly similar. Between the 2 treatment arms, trastuzumab deruxtecan was associated with higher grade 3-4 neutropenia and anemia. T-DM1 associated with higher grade 3-4 thrombocytopenia.

An adverse event of special interest is of course interstitial lung disease, and we did follow patients closely for this on this clinical trial. At our original reporting of DESTINY-Breast03, just over 10% of patients had any grade of interstitial lung disease, but there were no grade 4 or 5 events. With additional follow up and time on treatment, we now see about 15% of patients having any grade interstitial lung disease treated with trastuzumab deruxtecan. However, they're all grade 1 or 2 events. There were no additional grade 3 events, and still no grade 4 or 5 events. So in summary, these data really do underscore the activity and safety of trastuzumab deruxtecan when used in the second-line setting. These data support the use of trastuzumab deruxtecan instead of T-DM1 as a second line standard of care therapy after trastuzumab and a taxane.

Source:

Hurvitz S, Hegg R, Chung WP, et al. “GS2-02 - Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated survival results of the randomized, phase 3 study DESTINY-Breast03.” Presented at: San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas.