HER2+ mBC: Safety Outcomes From the DESTINY-Breast03 Trial

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Cynthia Lynch, MD: When you look at the total percentage of adverse drug events, about 98% of patients in the T-DXd group had drug-associated adverse event compared to 86.6% in the T-DM1 group. Of those, when you look at grade 3/4 adverse events, that occurred in about 45% of individuals with T-DXd versus 39.8% in those with T-DM1. An adverse event of special interest is the interstitial lung disease, or pneumonitis, associated with T-DXd. This was an adverse event that was known from the prior studies, and so this was of special interest. That did occur in approximately 10.5% of patients in the T-DXd group versus 1.9% in the T-DM1 group. When you look at the grade of those, the majority of those were a grade 2. Thankfully there were no grade 4/5 adverse events. It felt that perhaps it was because of being aware of this as the potential adverse event; medical oncologists were more aware of how to respond to that. Also, there was a lot of direction from the trial itself in how to address the appearance of drug-induced pneumonitis or interstitial lung disease. The median time to onset for interstitial lung disease was 168 days. It did result in discontinuation of therapy in about 8% of patients with T-DXd versus 1% in patients with T-DM1. The most common side effects associated with the T-DXd would be nausea, fatigue, vomiting, some alopecia as well, that was at 36%. There was some neutropenia and thrombocytopenia as well. Looking at always a concern of oncologists in individuals who are on trastuzumab type-directed therapies is looking at reductions in ejection fraction and that occurred in about 2.3% of individuals on the T-DXd versus 0.4% on the T-DM1 group.

In clinical practice, the most common side effects that I see associated with trastuzumab deruxtecan are the GI side effects of nausea. Typically, when I’m utilizing that drug, I do treat it as a highly emetogenic type regimen where I would be giving consideration for a drug such as palonosetron as well as Emend [aprepitant] along with the steroid. I have found that with the use of that combination of agents, patients typically do very well with that as long as they have as-needed rescue medicines too. I have had a few patients that have been a little more challenging, sometimes requiring dose reductions to address that, but I do think if oncologists are ready and understanding that it is a drug that can have a little bit higher level of nausea associated with it, it is something that can be very manageable. Fatigue, that’s so common with so many agents. I wouldn’t say this one necessarily causes more fatigue than others but that’s present. There can be some hair loss associated with it, that’s important for patients to be aware of. I will say overall when you look at cell counts, when you look for neutropenia, thrombocytopenia, and anemia, those are all fairly low occurrences that we would see associated with this drug. In fact, I’ve been impressed at how high the hemoglobins tend to run in patients who are receiving that agent.

With the drug trastuzumab deruxtecan, I’ll just emphasize that there is that risk of pneumonitis and interstitial lung disease. There have been deaths associated with that, so it is very important to be aware of that as a potential side effect to be sure to educate your patients about signs and symptoms of pneumonitis so that they can report that early. Also, to be aware, to be very quick to place that drug on hold if there is evidence on imaging of the development of pneumonitis there. I think that’s one of the things that really can help to protect patients who are receiving that agent; just being that heightened awareness of the risk of pneumonitis and jumping on treatment for it or holding drug at the first signs of its development.

Transcript edited for clarity.