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

Erika Hamilton, MD: Rita, we talked a bit of concerning the [adverse] results we generally see with tucatinib. What about trastuzumab deruxtecan [T-DXd]? What’s the distinction? What can we sometimes see there?

Rita Nanda, MD: The one factor sufferers will definitely speak about is the hair loss. We all know scalp cooling usually isn’t very efficient right here. [There is also] extra fatigue. I’ve undoubtedly seen some nausea with T-DXd, though it’s manageable. I’ve had 1 affected person who actually struggled with it, so I’d deliver her again periodically for IV [intravenous] fluids, however then over time, it simply acquired higher. I feel each [tucatinib and T-DXd are] tolerable [and] comparatively handy. You are available as soon as each 3 weeks. T-DXd [has] a bit of extra fatigue [and] extra nausea, after which tucatinib-based remedy [has] the hand-foot syndrome and diarrhea.

Erika Hamilton, MD: Completely. How do you are feeling about what we’ve seen up to date when it comes to ILD [interstitial lung disease] pneumonitis? Actually, primarily based on DESTINY-Breast01 [NCT03248492], [it] was a bit of extra of a priority for us as a result of we noticed deadly circumstances, however how are you feeling concerning the follow-up and the place we sit now?

Rita Nanda, MD: I’ve undoubtedly seen lower-grade ILD. We’re routinely checking imaging on these sufferers [with] a low threshold for working up any cough, shortness of breath, or hypoxia. I’ve been capable of maintain remedy and have the illness get higher, however it’s one thing we [must] be very vigilant about.

Erika Hamilton, MD: I agree. Ten % of sufferers is an honest quantity [who] may need some, however the truth that we’ve eradicated grade 4 and grade 5, and [the fact that] grade 3 is lower than 1%, makes me really feel a bit extra comfy with a number of the earlier trials. Tiffany, what do you consider for a affected person [who] has now progressed on T-DXd? The place do you go from there?

Tiffany Traina, MD: I’ll put in a plug for medical trials, that are at all times an important choice. It is determined by what these sufferers have beforehand seen as a result of, with DESTINY-Breast03 [NCT03529110] knowledge, T-DXd is in that second-line area now. A few of our sufferers [with] high-risk [disease] could have already seen [trastuzumab emtansine] and a la KATHERINE [NCT01772472], having failed pathologic [complete response] and have probably seen pertuzumab within the first-line setting. In [the] second-line, in the event that they’ve acquired tucatinib, I’m considering T-DXd afterward. In the event that they’ve acquired T-DXd within the second-line, tucatinib stays an important choice to succeed in for. Then past that, we nonetheless have brokers like margetuximab plus chemotherapy. We’ve different [tyrosine kinase inhibitors]—lapatinib/capecitabine [and] neratinib/capecitabine, [which are] supported by the NALA examine [NCT01808573]—[as well as] many new antibody-drug conjugates in improvement. Once more, a plug for these medical trials.

Erika Hamilton, MD: Completely. Rita, how do you consider sequencing? Are there any affected person traits that sway you in a single course vs one other?

Rita Nanda, MD: I’ll say it’s a dialog with sufferers. We’ve 2 medication related to a survival benefit within the second-line setting. Hair loss elements in and [so do] comorbidities or capsule burden. Some sufferers could not wish to take so many capsules on daily basis, and it’s exhausting for them. Coming in as soon as each 3 weeks for an [IV] infusion is way simpler for them. Actually co-pays think about, as properly, [because of] monetary toxicity for sufferers if they will’t afford these co-pays with the oral regimens. Then on the flip aspect, there are some people who don’t wish to lose their hair. The hand-foot syndrome is manageable. There’s not a lot in the way in which of diarrhea. Once more, it’s manageable. I feel it’s a dialog with sufferers to attempt to perceive what their objectives are and what [adverse] results they might be keen to place up with greater than others.

Erika Hamilton, MD: I feel very equally [as you do] on that. Realistically, our sufferers are in all probability going to get each of those [regimens]. I’m reassured by the truth that T-DXd had nice exercise, even in sufferers [who] are extra closely pretreated. If I could also be utilizing tucatinib as a result of any individual has mind metastases or they like to try this to keep away from hair loss, [then] I really feel very assured that T-DXd goes to work [in the] third-line [setting] or past, as properly. I feel it’s true. We’ve 2 brokers, and it’s an individualized resolution the way you would possibly sequence these.

Transcript has been edited for readability.