Advanced HER2-Positive Breast Cancer: Update on Destiny-Breast03 Data - Episode 4
Breast cancer experts, Sara Tolaney, MD, and Mark Pegram, MD, discuss current standard of care in sequencing of therapies in mBC and the effect of DESTINY-Breast03 data on sequencing going forward.
Sara Tolaney, MD: In my clinical practice, when using trastuzumab deruxtecan [T-DXd] we also have seen these really impressive response rates and rates of disease control. As was noted in DESTINY-Breast03 [DB03], the response rate was about 80%. The complete response rate was about 16%. We’ve never seen a complete response rate this high, suggesting that this agent may be allowing some patients to have very durable disease control. In fact, many of us wonder if some of these patients in CR [complete remission] could be cured. When treating patients [with] trastuzumab deruxtecan, I think one toxicity that we do have to be aware of is risk of interstitial lung disease [ILD]. Previously, in DESTINY-Breast01, we had seen that there was about a 15% rate of ILD in this pretreated patient population. In DESTINY-Breast03, which is less pretreated patients, we saw a lower rate of ILD of about 10%. Importantly, in this trial we saw no grade 4 or grade 5 ILD and there were only 2 cases of grade 3 ILD. What you’re seeing is that most of the ILD that occurs is occurring at a grade 1 or 2 level. Our group has put into place making sure that we make all patients aware of the risk of ILD so that if, for example, they develop any symptoms like shortness of breath, cough, dyspnea on exertion that we’re able to work them up very quickly. Usually getting a high-resolution CT [computed tomography scan] would be advised for workup and potentially considering infectious allergies and those out. We have also put in place routine pulse oximeter monitoring for all our patients getting T-DXd. Our group has started scanning these patients every 6 weeks as had been done in DESTINY-Breast01 as well as DESTINY-Breast03. The idea being that we may be able to pick up those low-grade ILDs on these routine scans. Doing them on a regular basis may help pick those up potentially earlier so that you can intervene if needed. Other toxicities to think about include risk of some fatigue and some nausea. I give my patients prophylactic antiemetics with the infusion and I give them antiemetics that they can use as needed over the course of treatment because I can see some low-grade delayed nausea. It is important to warn patients that there is a risk of alopecia, although, as we saw in DESTINY-Breast03, that was about 30%, so not the majority of patients but important to note. You can sometimes see some neutropenia so it’s important to monitor for that in these patients.
Mark Pegram, MD: My experience with T-DXd is that in contrast to T-DM1 [ado-trastuzumab emtansine] it does have more chemotherapy-like side effects. It is very important to advise patients that this is the case. They should not expect an experience that is similar to T-DM1 in patients that may have had prior T-DM1 treatment either in the post neoadjuvant setting or in the metastatic disease setting. Rather it does have chemo side effects like nausea/vomiting, which does require some premedication with antiemetics routinely. Then also, one must be mindful of the drug-induced pneumonitis issues since there are very strict guidelines in the prescribing information that one must follow in terms of dose interruption and consideration of steroids or even drug cessation depending on the severity of drug-induced pneumonitis. But overall, this drug is quite well tolerated as metastatic breast cancer drugs are concerned. It’s arguably somewhat less toxic than many of our cytotoxic chemotherapy drugs or chemotherapy combinations. It’s not quite as easy to take as T-DM1 for example. I don’t have much experience personally with drug-related pneumonitis mainly because it’s fairly infrequent. I’ve seen 1 case of a grade 1 event. That patient was progressing in the brain at the same time and consequently we discontinued T-DXd in that case. The ILD resolved and was no further consequence in that particular patient. Overall, based on the strength of the DB03 data this, this T-DXd agent is associated with such robust efficacy signals that it must be considered moving up from a third or a later line consideration into a second or later line consideration based on the strength of the DB03 data in my opinion.
Transcript edited for clarity.