Trastuzumab deruxtecan effective against brain metastases in HER2-positive breast cancer

Dr Nancy Lin - Dana-Farber Cancer Institute, Boston, USA

DESTINY-Breast12 is a prospective study, non-randomised, that included two cohorts of patients: patients with baseline brain metastases, which could be either stable or active, and patients without brain metastases.

What was the methodology?

The primary endpoint in the brain metastasis cohort was progression free survival, and the primary endpoint in the non-brain metastasis cohort was overall response. Patients were followed using RECIST 1.1 by independent central review, and if a patient had brain metastases they could be counted towards the assessment of both overall response and CNS response.

What were the primary results?

The primary results in the brain metastasis cohort was that the 12-month PFS rate was 61%, and the median PFS was 17.3 months. If we look at the intracranial response rates, it was 71% overall. It was actually 79% in patients with stable brain mets and 62% in patients with active brain mets. Interestingly, in the subset of patients with untreated active brain mets, the CNS response rate was 82%. In the non-brain met cohort, the response rates were really similar and in line with what we’ve seen in other T-DXd trials, and the median duration of response was not reached.

What was the toxicity profile?

The toxicity profile included nausea, fatigue, similar to what we’ve seen in other T-DXd studies. The two cohorts were not formally compared as far as the toxicity profiles, but overall, qualitatively they look similar. It didn’t look like the brain metastasis patients experienced dramatically different toxicities than non-brain-metastasis patients. The main AE of interest was ILD, interstitial lung disease, and there were unfortunately six deaths from interstitial lung disease in the brain met cohort, and three deaths in the non-brain met cohort. It’s important to note that this was not independent ILD committee adjudicated events, and in fact four of the six grade 5 events in the brain metastasis cohort were co-occurring with opportunistic infections including pneumocystis, pneumonia and aspergillosis.

What impact might this study have?

I think this really provides evidence where we previously had a gap, particularly in patients with active brain metastases, because there were over 100 such patients included in the study, and over 250 patients altogether with brain metastasis in the cohort. I think it really solidifies the role of T-DXd, not only for patients without brain metastasis in the second-line setting, but now I think launches it as a very reasonable option in the second-line setting for patients with brain metastases, whether or not they’re stable or active.