Sequencing Therapy in MBC in Second Line and Beyond


Closing out their conversation on the first patient profile, oncology nurse experts consider sequencing therapy following trastuzumab deruxtecan in both breast and GI cancers.


Sarah Donahue, MPH, NP, AOCNP: In the second-line setting, there are a lot of options out there. We just talked about a patient who may not be able to tolerate trastuzumab deruxtecan because of their lung issues. But let’s say they don’t have any lung issues, and you’re trying to choose what to use. Are you now using trastuzumab deruxtecan as your second line? Is that what you’re seeing in breast cancer, Jamie?

Jamie Carroll, APRN, CNP, MSN: Yeah, absolutely. With new data coming out from the DESTINY-Breast03 study, we’ve moved up trastuzumab deruxtecan to the second line. Then the question is, what about in the third line and beyond? What do you use there? It’s dealer’s choice, right? Once a patient is having progression on trastuzumab deruxtecan, do we use T-DM1 [trastuzumab emtansine]? Previously, T-DM1 [trastuzumab emtansine] was the second line, and then we thought of trastuzumab deruxtecan in the third line. But we don’t have data. If we move trastuzumab deruxtecan to the second line, we don’t know how effective T-DM1 [trastuzumab emtansine] will be after progression on trastuzumab deruxtecan.

Additionally, we’ve got TKIs [tyrosine kinase inhibitors]: tucatinib-capecitabine-trastuzumab, lapatinib-capecitabine-trastuzumab. The landscape of HER2 [human epidermal growth factor receptor 2]–positive breast cancer has changed significantly in the last couple of years, and it’s opened up options for our patients, which is awesome.

Sarah Donahue, MPH, NP, AOCNP: It’s definitely opened up many options. What about with patients with progressive brain metastases? Do you have a preference for using trastuzumab deruxtecan over tucatinib-capecitabine-trastuzumab if you were at that point?

Jamie Carroll, APRN, CNP, MSN: That’s a great question. We tend to use tucatinib, knowing that it’s going to penetrate the blood-brain barrier. I’ve seen patients who have active brain metastases get smaller with tucatinib after a short period of time. I had 1 patient who unfortunately lost her insurance and ran out of tucatinib. Eleven days later, she had progressive brain metastases, so I knew it was working effectively in her. That’s the choice that I would have with brain metastases.

Sarah Donahue, MPH, NP, AOCNP: In gastric cancer, what line is the trastuzumab deruxtecan? Liz?

Elizabeth Prechtel Dunphy, DNP, CRNP, AOCN: Insecond-line therapy, usually following a progression of fluoropyrimidine, something like FOLFOX—5-FU [5-fluorouracil], leucovorin, oxaliplatin—potentially with pembrolizumab if they have PD-L1 positivity or an increased CPS [cognitive performance scale] score.

Transcript edited for clarity.

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