Research Efforts in HER2+ Breast Cancer Pick Up Speed Despite COVID-19

Beyond the addition of novel agents such as fam-trastuzumab deruxtecan-nxki (Enhertu) and tucatinib (Tukysa) to the HER2-positive treatment armamentarium, several efforts are underway to examine novel combinations, CDK4/6 inhibitors, and more, despite the challenges posed by the COVID-19 pandemic, according to Jane L. Meisel, MD.

“During this year, which has been a tough for a lot of people, it's very exciting just to see so much research continue to be reported and be presented,” Meisel said. “Many people worried, and rightly so, that cancer research would really fall behind during this time of national and international crisis, and seeing these studies continue to push forward, and progress continue to be made, is just very heartening.”

In an interview with OncLive^® during an Institutional Perspectives in Cancer webinar on Breast Cancer, Meisel, an associate professor for the Departments of Hematology and Medical Oncology, and Gynecology & Obstetrics at Winship Cancer Institute, Emory University School of Medicine, discussed sequencing questions, tucatinib combinations under exploration, and emerging strategies for use in the treatment of patients with HER2-positive breast cancer.

OncLive^®: In the metastatic setting, we have the phase 2 DESTINY-Breast01 (NCT03248492) and HER2CLIMB (NCT02614794) trials. Based on the data observed so far, what is known in terms of sequencing?

Meisel: It’s still very clear that a taxane plus pertuzumab/trastuzumab is our first-line option, and for most patients, T-DM1 is still a second-line option. The one exception to that might be if someone recurs with a significant amount of brain disease and not as much disease systemically. You would have the option, based on the FDA approval, to use tucatinib, trastuzumab, and capecitabine before T-DM1, because there was such impressive brain metastases data in the HER2CLIMB study. Deliberately, the approval was for [use in the] second-line [setting] or [later], even though the study was done in the third-line [setting] or [later].

For most patients [who need treatment] in the third line, we have options. I tend to use the tucatinib/trastuzumab/capecitabine option, the HER2CLIMB regimen, as my go-to third-line approach just because I like the idea of doing something after T-DM1 that's not also an antibody-drug conjugate. I like the idea that there's a TKI and a little bit of chemotherapy for those more heterogeneous patients.

I can see situations in which you get such great, fast, and solid responses with the HER2CLIMB regimen that potentially using that drug earlier on could be attractive in a patient whose systemic disease is really taking off in the third line. One doesn’t necessarily have to come before the other in 100% of cases, but we have many great options and the ability to optimize care for each patient.

Ongoing studies are examining tucatinib in combination with T-DM1 and fam-trastuzumab deruxtecan-nxki (Enhertu). Do you have any inclination as to whether one agent might synergize better with tucatinib than the other?

It's hard to know since they're not head-to-head trials. We may end up needing to look at safety profiles to see whether one dovetails more safely with tucatinib than the other. Do we need to do that at all? One of the concerns I have about potentially doing too much too soon is, do you spend all the chips that you have? Or might it be better to do things one at a time and save some options for later? It will be interesting to see how patients respond, what the response rates are, the safety profiles, and what the quality-of-life [QoL] aspects are.

Are you hopeful that CDK4/6 inhibitors will enter the HER2-positive paradigm?

At some points in their [treatment] course, patients may require more of an endocrine-directed type of [approach]. We saw in the monarcHER trial [NCT02675231], that adding abemaciclib [Verzenio] to trastuzumab and fulvestrant helped improve outcomes over trastuzumab plus chemotherapy alone and was better tolerated. CDK4/6 inhibitors will make their way into this space. It'll be very interesting to see, with the PATINA trial [NCT02947685], whether palbociclib [Ibrance] is able to make its way into first-line maintenance for the estrogen receptor [ER]–positive/HER2-positive cohort.

What were some of the key updates reported at the 2020 San Antonio Breast Cancer Symposium that caught your attention?

A lot of exciting [news] came out of [the meeting]. I was particularly interested in the [focus of] refining immunotherapy for triple-negative breast cancer. There's so much about QoL for these patients and which patients should be chosen for these immunotherapy regimens that we still don't [fully understand]. Every step forward that we get in terms of clarity on that piece [of the puzzle] helps us.

Then, of course, [we saw] RxPONDER, and [we have] more clarity on these [patients with] node-positive, ER-positive breast cancer, particularly those who are postmenopausal. Now, we know we've got another subset of patients for whom we can potentially omit chemotherapy. It’s always exciting to be able to do something less toxic and say with certainty that we're doing it safely.