T-DXd Shows Promise in Treating HER2+ Breast Cancer With Brain Mets

The phase 3b/4 DESTINYBreast-12 study (NCT04739761) assessed the efficacy and safety of trastuzumab deruxtecan (T-DXd; Enhertu) in patients with HER2+ metastatic breast cancer. Participants were divided into two groups: those with stable or active brain metastases (BM cohort) and those without BM.

The primary endpoints were progression-free survival (PFS) for the BM cohort and objective response rate (ORR) for the non-BM cohort. Secondary endpoints included CNS PFS, CNS ORR, and safety.

Results showed that T-DXd demonstrated significant and durable clinical activity in both groups, including intracranial activity. The BM cohort had a 12-month PFS of 61.6%, and the non-BM cohort had a 12-month ORR of 62.7%.

The most common adverse event was interstitial lung disease/pneumonitis, occurring in 16% of the BM cohort and 12.9% of the non-BM cohort.

Overall, T-DXd appears to be a promising treatment option for patients with HER2+ metastatic breast cancer, especially those with stable or active BM.

Here, Nancy Lin, MD, professor of medicine, Harvard Medical School, and medical oncologist, Harvard Cancer Institute, in Boston, Massachusetts, discusses the efficacy of T-DXd for brain metastases compared with other agents.

Transcription:

0:05 | The other agent that comes top of mind is tucatinib [Tukysa], either tucatinib with trastuzumab [Herceptin] or tucatinib with T-DM1 [trastuzumab emtansine; Kadcyla], as was shown in both HER2CLIMB [NCT02614794] and then HER2CLIMB-02 [NCT03975647]. The patient populations in HER2CLIMB are different from [DESTINYBreast-12 (DB-12)]. HER2CLIMB enrolled patients who had to have had trastuzumab, protuzumab, T-DM1, whereas in DB-12, only 40% of patients had had prior T-DM1. So we have to be a little careful with cross-talk comparisons. Having said that, the median PFS in HER2CLIMB among the brain met population is just over 7 months and intracranial response rate was around 50%.