Advances in Treating HER2+ Breast Cancer With Brain Metastases

Sarah Sammons, MD, medical oncologist, clinical investigator in the Breast Oncology Center, associate director of the Metastatic Breast Cancer Program, Dana-Farber Cancer Institute, discusses findings from an analysis of the DESTINY-Breast03 trial (NCT03529110) regarding trastuzumab deruxtecan (Enhertu; T-DXd) vs trastuzumab emtansine (Kadcyla; T-DM1) in the context of HER2-positive breast cancer with brain metastases.

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0:09 | [In] the DESTINY-Breast03 clinical trial, they did allow patients who had a history of stable brain metastasis on the trial. Stable means that they had had prior radiation, and their brain metastasis were not progressing. There are a handful of patients in DESTINY-Breast03 with active brain metastasis that were enrolled, and they did look and see how both the stable and active [patients with] brain metastasis did on the trial with T-DXd vs T-DM1. We recently saw those results that were published in [European Society for Medical Oncology (ESMO) Open].

0:54 | Essentially, what we saw was that the patients with a history of brain metastasis did incredibly well with T-DXd, and they did better with T-DXd than with T-DM1. In terms of progression-free survival, the patients with a history of brain metastases had a progression-free survival of 15 months with T-DXd vs 3 months with T-DM1, so a dramatic benefit.

1:21 | The authors and [principal investigators] of the study also retrospectively looked at the MRIs of the patients that had a history of brain metastasis in DESTINY-Breast03, and they looked to see what the intracranial response rate was, so what was the number of patients who had their brain metastasis either go away completely, a complete response, or shrink by about 30% in the brain, and they reported an intracranial response rate of almost 66% with T-DXd vs 34% with T-DM1.

2:02 | So, 66% in terms of an intracranial response rate is very high and really the highest that we have ever seen for an antibody-drug conjugate, or really any therapy in HER2-positive [breast cancer with] brain metastasis. That is exciting news for these patients, and it makes T-DXd an excellent option for patients with either stable or active HER2-positive brain metastasis.

2:33 | Another thing that I want to point out is that T-DM1, which is kind of our older antibody-drug conjugate, still had an intracranial response rate of 34%, which is pretty high too. Just to put it all in context, in metastatic breast cancer with standard chemotherapies, we are used to intracranial response rates around 10%. So, what this has shown us is that antibody-drug conjugates, both T-DM1 and trastuzumab deruxtecan, do seem to get into the brain quite well, which opens up future research in this hot category of drugs called antibody-drug conjugates for the treatment of really all [patients with] metastatic breast cancer with brain metastasis. Even in other solid tumors, I think ADCs are a promising strategy.