Spotting the exceptional responders

The latest research on HER2-positive breast cancer was presented at the Gathering Around Cancer Conference by Dr Sonya Chew of University Hospital Galway.

Dr Chew has recently returned to Ireland following a Fellowship at the Memorial Sloan Kettering Cancer Centre, New York, US.

She presented an overview of selected clinical trials published in the past year, such as the KATHERINE trial, as well as the DESTINY-12 and HER2CLIMB studies.

Dr Chew discussed the early breast cancer setting, as examined in the KATHERINE trial, which looked at T-DM1 in patients who have residual disease after neoadjuvant treatment and where patients were divided between T-DM1 or trastuzumab alone. “We see that brain metastases occur equally in both arms, which shows that we still need newer, further agents to help prevent this.”

She added: “Adjuvant T-DM1 improved invasive disease-free survival and overall survival in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant therapy.”

Dr Chew said a critical question in this field of treatment is how to identify and predict which patients will be exceptional responders to therapy, and particularly patients who do well on first-line therapy.

She presented data from a French national cohort study on first-line anti-HER2 therapy in the metastatic setting between 2008 and 2021. The criteria included five years of follow-up with no progression. “In this retrospective study, they found that close to 25 per cent of women with HER2-positive metastatic breast cancer had an exceptional response with their first-line treatment,” said Dr Chew. “…. The exceptional responders had an almost 70 per cent chance of remaining progression-free at five years.” The predictive variables for exceptional responders include if they are HR-negative, have non-visceral disease, and are strongly HER2-positive.

Dr Chew discussed the DESTINY-12 trial, which looked at administering trastuzumab deruxtecan (T-Dxd) to patients with HER2-positive disease with and without brain metastases. Patients with active brain metastases were also included, meaning patients who had brain metastases that had not been treated before, or those who had previously-treated brain metastases that were progressing.

“When you look at patients who had active or stable brain metastases, the efficacy seemed to be relatively the same,” said Dr Chew. “When you break it down, in the active brain metastases group, both types of untreated or previously-treated groups seemed to benefit. For progression-free survival, the 12-point mark was also impressive at close to 58 per cent. For overall survival, comparing both of the groups, both had close to 90 per cent at the one-year mark,” although she cautioned the current data is still immature.

“T-Dxd has shown overall a durable response and intracranial clinical activity in a large patient cohort with HER2-positive and metastatic breast cancer with stable and active brain metastases,” said Dr Chew. “We do have some trials coming in 2025 that will be interesting to follow in the HER2-positive space.” Some of these studies will examine T-Dxd in the first-line setting, which could have clinical as well as longer-term healthcare economics benefits, she concluded.