NEW YORK – In the DESTINY-Breast12 trial, AstraZeneca and Daiichi Sankyo's antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) showed efficacy in a large cohort of previously treated patients with HER2-positive metastatic breast cancer who have brain metastases.
At the European Society for Medical Oncology Congress on Friday, researchers shared data from the Phase IIIb/IV trial, which included the largest cohort, 263 patients, with brain metastases who had received Enhertu to date. The results, simultaneously published in Nature Medicine, strengthen oncologists' understanding of Enhertu's clinical activity as a second-line option for metastatic breast cancer, experts at the meeting in Barcelona said.
About half of the patients with HER2-positive metastatic breast cancer will develop brain metastases, Nancy Lin, associate chief of the division of breast oncology at Dana-Farber Cancer Institute, said during a presentation of the DESTINY-Breast12 results at the meeting on Friday. The trial included those with stable brain metastases at baseline after prior treatment as well as patients with active brain metastases, including both patients who were treatment naïve and previously treated but progressing.
Other treatment regimens, such as Seagen's tyrosine kinase inhibitor Tukysa (tucatinib) plus Genentech's ADC Kadcyla (ado-trastuzumab emtansine), have shown efficacy in this patient population. For example, in the HER2CLIMB-02 trial, metastatic HER2-positive breast cancer patients with brain metastases had a median progression-free survival of 7.8 months on the Tukysa-Kadcyla-chemo combo.
Still, there is a need for more effective treatments for patients whose breast cancers have spread to the brain. Enhertu has been an option for heavily pretreated, unresectable or metastatic HER2-positive breast cancer patients since 2019, but previous studies have only explored its efficacy treating those with brain metastases in small cohorts or retrospective studies, Lin said.
In the DESTINY-Breast12 trial, the cohort of patients with baseline stable or active brain metastases had a median progression-free survival of 17.3 months on Enhertu, with 61.6 percent of patients living a year without their disease progressing. Lin noted that the 12-month progression-free survival rate was consistent across patients with stable brain metastases and active brain metastases who were previously treated. However, the active, or progressing, previously untreated brain metastases group did have a numerically lower 12-month progression-free survival rate compared to the overall brain metastases cohort, she added, but the number of progression events in this group was low.
The central nervous system 12-month progression-free survival rate was also consistent across the stable and active brain metastases groups at 58.9 percent.
In the entire brain metastases cohort, half of the patients, 51.7 percent, responded to Enhertu, with 11 patients experiencing a complete response. The intracranial response rate in these patients with stable or active brain metastases was 71.7 percent.
More patients with stable brain metastases had an intracranial response on Enhertu compared to those with active brain metastases, 79.2 percent versus 62.3 percent, respectively. In a post hoc analysis, the researchers compared intracranial responses among patients with active brain metastases based on whether they were untreated or previously treated. There was an 82.6 percent intracranial response rate in the untreated group with active brain metastases, while only half of the patients in the previously treated, progressing group had an intracranial response.
The DESTINY-Breast12 study also included a cohort of patients without brain metastases, who demonstrated response rates and survival outcomes in line with previous studies of Enhertu in HER2-positive metastatic breast cancer. Lin also noted that the 12-month overall survival rate was similar between the cohort with brain metastases and the cohort without, with about 90 percent of patients living at least 12 months in both groups. Median overall survival was not reached at the time of data cutoff with around 15 months of follow-up.
These data are "very promising for this population of patients with a historically poor prognosis," Cristina Saura Manich, head of the breast cancer unit within the service of medical oncology at Vall d'Hebron University Hospital in Barcelona, said in a discussion of the DESTINY-Breast12 results.
"The population that interests us the most are those with active brain metastasis [who] are often symptomatic," Manich said. "The response rate of almost 83 percent in these previously untreated patients [in DESTINY-Breast12] is particularly interesting." Manich added that the data reinforces her preference for systemic treatment of brain metastases and delaying radiotherapy until later stages of the disease.
Based on the data from DESTINY-Breast12, Manich concluded that Enhertu should be the "preferred option" for second-line treatment of HER2-positive metastatic breast cancer, regardless of whether the patient has brain metastases.