Standard of Care for R/R Metastatic HER2+ Breast Cancer

Giuseppe Curigliano, MD, PhD: We have several options for patients progressing on the standard of care, which was trastuzumab, pertuzumab, and taxanes in the first line and T-DM1 [trastuzumab emtansine] in the second line. After progression on those agents, we have several options. One option is trastuzumab, capecitabine, and tucatinib. Because according to the data from the HER2CLIMB trial, we had a dramatic improvement in terms of progression-free survival and overall survival.

We also have data from the DESTINY-Breast01 trial in which there was a dramatic benefit derived from trastuzumab deruxtecan. But since we have evidence from a prospective randomized trial, we should take into account the probability to use tucatinib in the third-line setting, because we can also use trastuzumab deruxtecan later. We’re going to have the data from DESTINY-Breast03 during ESMO [European Society for Medical Oncology Congress] 2021, and it will be really important to understand the results and the margin of benefit of trastuzumab deruxtecan in order to generate another algorithm for this patient population.

I don’t believe HR [hormone receptor] status is a predictive factor of benefit. If we look at the subgroup analysis in the context of the HER2CLIMB, we had a similar benefit in both the HR-positive and HR-negative subgroups.

The only study to assess the large number of patients with active brain metastases was HER2CLIMB. It’s quite clear in the context of HER2CLIMB that there’s an impressive benefit in terms of both progression-free survival and overall survival. If you have brain metastases, you should consider the use of the combination of tucatinib, capecitabine, and trastuzumab in your treatment algorithm—we have level 1 evidence with a grade of recommendation A because we had a prospective randomized trial.

Of course, HER2CLIMB was designed for patients with visceral disease as well. Even if we have data that are a little different between bone-only disease and visceral disease, the overall survival benefit in the HER2CLIMB study was in the intent-to-treat population. You have an overall survival benefit in all the populations. I believe this type of combination should be considered according to the evidence of the prospective randomized trial.

Transcript edited for clarity.