DESTINY-Breast04: T-DXd in HER2-Low Metastatic Breast Cancer
Following her review of TROPiCS-02, Joyce O’Shaughnessy, MD, shares data from the DESTINY-Breast04 study of T-DXd in HER2-low metastatic breast cancer.
Transcript:
Joyce A. O’Shaughnessy, MD: And then [there is the phase 3] DESTINY-Breast04 [trial; NCT03734029], which everyone’s well aware of, for HER2-low, 1+ or 2+ IHC [immunohistochemistry], FISH [fluorescence in situ hybridization]-negative patients who had 1 prior line of chemotherapy in the metastatic setting. Mostly HR [hormone receptor]-positive, HER2-negative [patients], but there were 58 patients that were triple-negative. They were [randomly assigned] to trastuzumab deruxtecan. Again, now targeting HER2-low and conjugated to deruxtecan, the very powerful topoisomerase I inhibitor. Every 3-week, weekly therapy. We’re all very familiar. Versus quite a variety of choices on single-agent chemotherapy with a primary end point of progression-free survival in the HR-positive population. So, the HR-positive population was the vast majority, and so all patients in HR-positive, they’re very similar. And these patients had liver metastasis, but not quite as common as in the [phase 3] TROPiCS-02 [trial; NCT03901339], but about 70% had liver metastasis. And in terms of prior therapies, 70% had a prior CDK4/6 inhibitor, unlike [in] TROPiCS-02, which was 100%, and median number of lines of prior chemotherapy in the metastatic setting was 1. And if we look at the top left, at PFS [progression-free survival] in the HR-positive patients, down the bottom left, overall survival, we really saw very substantial improvement in progression-free survival from 5.4 to 10 months, as well as about a 6.4-month improvement in overall survival from 17 to 24 months in the HR-positive [group]. It’s pretty well-reflected similarly in the all-patient population as well. Response rates were substantially higher. We can see here over on the right; we’ve got the triple-negative patients over on the right. And you can see on the top, we’re looking across at response rates; with chemotherapy was about 16% regardless of triple-negative or HR-positive, and it was about 50%. So, dramatically higher response rates with the trastuzumab deruxtecan. The main toxicities here are nausea, which can be low-grade and chronic. And olanzapine, 2.5 mg at bedtime, is magical to get rid of that chronic nausea. Some fatigue, but not really different than the chemotherapy. There is some alopecia, not much at all in the way of myelosuppression or issues with the liver. Down the bottom, the main other toxicity we need to watch out for is ILD [interstitial lung disease]; 12% of the patients had ILD. There were 3 deaths, unfortunately, with ILD in DESTINY-Breast04.
Transcript is AI-generated and edited for clarity and readability.
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