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ASCO 2021 | Trastuzumab deruxtecan in patients with breast cancer and brain metastases in DESTINY-Breast01

Guy Jerusalem, MD, PhD, Domaine Universitaire du Sart Tilman, Liège, Belgium, discusses the efficacy of trastuzumab deruxtecan (T-DXd) in a subgroup analysis of patients with breast cancer and brain metastases in the Phase II DESTINY-Breast01 trial (NCT03248492). Patients enrolled in DESTINY-Breast01 had HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab emtansine. 24 patients with a history of brain metastases at baseline were included in the subgroup analysis. It was shown that the overall response rate, median progression-free survival, and median duration of response in patients with brain metastases were comparable to the overall population. Baseline diameter data was assessed where available, which showed a central nervous system (CNS) response rate of 50%. Overall, T-DXd showed strong clinical activity in patients with breast cancer and brain metastases and the demonstrated CNS response warrants further investigation. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.

Transcript (edited for clarity)

In the DESTINY-Breast01 trial, patients have advanced HER2+ breast cancer. They all received trastuzumab deruxtecan at the recommended dose of 5.4 milligram per kilogram. And, in this ASCO presentation, we looked in particular into the subgroup of patients who had a history of brain metastases. So, 24 patients actually, and only 184. The important these patients have no active symptomatic brain metastases, because here we are still waiting to have an idea how the drug works...

In the DESTINY-Breast01 trial, patients have advanced HER2+ breast cancer. They all received trastuzumab deruxtecan at the recommended dose of 5.4 milligram per kilogram. And, in this ASCO presentation, we looked in particular into the subgroup of patients who had a history of brain metastases. So, 24 patients actually, and only 184. The important these patients have no active symptomatic brain metastases, because here we are still waiting to have an idea how the drug works. So, a concern in these 24 patients, actually 17 had still lesions present when they entered the clinical trial. For 15 of the 17, we have the possibility to have resided concerning efficacy. And, we’ve seen that among the 15 patients, seven presented had a partial response, seven have stable disease, and one has only a progression of the disease. This is in particular concerning the in brain outcome of the treatment.

It’s important to mention the overall response rate was about 60% in the CNS subgroup, which is similar to what has been seen in the whole patient population. Also, the duration of the responses was extremely long. It was almost 17 months in the CNS subgroup, about 15 months in the whole patient population. But, I should mention that all these patients that received prior treatment with T-DM1, and they had received a median of six prior lines of treatment. So, seeing this long duration of response is really exciting.

Also, when we look to the median progression for survival in the patients with brain metastases, it was a little bit more than 18 months. So again, really impressive if you take into account all the previous treatment. And then, the last point concerns the new events in the brain. And, here we have seen a total of four events in the 184 patients. Two were in the CNS subgroup.

Here this was early events within the first three months. But, we’ve also seen two events in the non-CNS subgroup. And, there we saw late events after more than 300 and almost 500 days after entering the clinical trial. The limitation of this presentation, of course, is the low number of patients with brain lesions, 24. And, this was a post hoc analysis. So, now there are four additional trials ongoing. Including two very large international trials, where we are looking not only to patients with a history of brain metastases, but also patient with active brain metastases. In addition, we also looking to combination of trastuzumab deruxtecan with tucatinib, in particular. And then, we also not restricting only to patients with HER2-positive disease, but also patient with HER2-low expressing tumors, because there also could be an interesting response. And finally, in some of these trials, we are also looking to patients with leptomeningeal carcinomatosis . So, this is a very poor disease situation. And also, there maybe there is an interest to use this drug.

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Disclosures

Dr. Jerusalem reports personal fees and non-financial support from Novartis, during the conduct of the study: grants, personal fees and non-financial support from Novartis, grants, personal fees and non-financial support from Roche, grants, personal feed and non-financial support from Pfizer, personal fees and non-financial support from Lilly, personal fees and non-financial support from Amgen, personal fees and non-financial support from BMS, personal feed and non-financial support from Astra-Zeneca, personal fees from Daiichi Sankyo, personal fees from Abbvie, non-financial support from Medimmune, non-financial support from MerckKGaA.

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