Improving Outcomes in Patients With HER2+ Metastatic Breast Cancer: Applying Evidence to Clinical Practice - Episode 7

Selecting and Sequencing Tucatinib and T-DXd in HER2+ BC and Brain Metastases

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Centralizing the conversation on trastuzumab deruxtecan, panelists comment on treatment toxicity and factors to consider when sequencing therapies in later lines of treatment.

Erika Hamilton, MD: Rita, we talked a little about the [adverse] effects we commonly see with tucatinib. What about trastuzumab deruxtecan [T-DXd]? What’s the difference? What do we typically see there?

Rita Nanda, MD: The one thing patients will certainly talk about is the hair loss. We know scalp cooling generally isn’t very effective here. [There is also] more fatigue. I’ve definitely seen some nausea with T-DXd, although it’s manageable. I’ve had 1 patient who really struggled with it, so I would bring her back periodically for IV [intravenous] fluids, but then over time, it just got better. I think both [tucatinib and T-DXd are] tolerable [and] relatively convenient. You come in once every 3 weeks. T-DXd [has] a little more fatigue [and] more nausea, and then tucatinib-based therapy [has] the hand-foot syndrome and diarrhea.

Erika Hamilton, MD: Absolutely. How do you feel about what we’ve seen updated in terms of ILD [interstitial lung disease] pneumonitis? Certainly, based on DESTINY-Breast01 [NCT03248492], [it] was a little more of a concern for us because we saw fatal cases, but how are you feeling about the follow-up and where we sit now?

Rita Nanda, MD: I’ve definitely seen lower-grade ILD. We’re routinely checking imaging on these patients [with] a low threshold for working up any cough, shortness of breath, or hypoxia. I’ve been able to hold therapy and have the disease get better, but it is something we [must] be very vigilant about.

Erika Hamilton, MD: I agree. Ten percent of patients is a decent amount [who] might have some, but the fact that we’ve eliminated grade 4 and grade 5, and [the fact that] grade 3 is less than 1%, makes me feel a bit more comfortable with some of the earlier trials. Tiffany, what do you think about for a patient [who] has now progressed on T-DXd? Where do you go from there?

Tiffany Traina, MD: I’ll put in a plug for clinical trials, which are always a great option. It depends on what these patients have previously seen because, with DESTINY-Breast03 [NCT03529110] data, T-DXd is in that second-line space now. Some of our patients [with] high-risk [disease] may have already seen [trastuzumab emtansine] and a la KATHERINE [NCT01772472], having failed pathologic [complete response] and have likely seen pertuzumab in the first-line setting. In [the] second-line, if they’ve received tucatinib, I’m thinking T-DXd afterward. If they’ve received T-DXd in the second-line, tucatinib remains a great option to reach for. Then beyond that, we still have agents like margetuximab plus chemotherapy. We have other [tyrosine kinase inhibitors]—lapatinib/capecitabine [and] neratinib/capecitabine, [which are] supported by the NALA study [NCT01808573]—[as well as] many new antibody-drug conjugates in development. Again, a plug for those clinical trials.

Erika Hamilton, MD: Absolutely. Rita, how do you think about sequencing? Are there any patient characteristics that sway you in one direction vs another?

Rita Nanda, MD: I will say it’s a conversation with patients. We have 2 drugs associated with a survival advantage in the second-line setting. Hair loss factors in and [so do] comorbidities or pill burden. Some patients may not want to take so many pills every day, and it’s hard for them. Coming in once every 3 weeks for an [IV] infusion is much easier for them. Certainly co-pays factor in, as well, [because of] financial toxicity for patients if they can’t afford those co-pays with the oral regimens. Then on the flip side, there are some individuals who don’t want to lose their hair. The hand-foot syndrome is manageable. There’s not much in the way of diarrhea. Again, it’s manageable. I think it’s a conversation with patients to try to understand what their goals are and what [adverse] effects they may be willing to put up with more than others.

Erika Hamilton, MD: I think very similarly [as you do] on that. Realistically, our patients are probably going to get both of these [regimens]. I’m reassured by the fact that T-DXd had great activity, even in patients [who] are more heavily pretreated. If I may be using tucatinib because somebody has brain metastases or they prefer to do that to avoid hair loss, [then] I feel very confident that T-DXd is going to work [in the] third-line [setting] or beyond, as well. I think it is true. We have 2 agents, and it’s an individualized decision how you might sequence those.

Transcript has been edited for clarity.