Trastuzumab-deruxtecan showed clinical activity in patients with brain metastases

A subgroup analysis of the DESTINY-Breast01 trial demonstrated clinical activity of the antibody-drug conjugate trastuzumab-deruxtecan (T-DXd) in patients with HER2-positive metastatic breast cancer who presented with baseline brain metastases.

Patients with HER2-positive metastatic breast cancer are at high risk of developing brain metastases, and treatment options are limited once brain metastases occur [1]. T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a topoisomerase I inhibitor payload [2].

In the ongoing, phase 2 DESTINY-Breast01 trial (NCT03248492), 184 patients with HER2-positive metastatic breast cancer were enrolled, of whom 24 had a history of brain metastases (17 had brain lesions at baseline). Patients received T-DXd at 5.4 mg/kg every 3 weeks. Overall, T-DXd showed durable anti-tumour activity, and these results led to the approval of T-DXd for the treatment of adult patients with HER2-positive, unresectable or metastatic breast cancer who received 2 or more prior anti-HER2-based regimens (USA and Europe) or had prior chemotherapy and are refractory to or intolerant of standard treatments (Japan) [3].

Prof. Guy Jerusalem (CHU Liège, Belgium) presented the results of a subgroups analysis of the 24 patients with baseline brain metastases [4]. Brain lesions were monitored by MRI or CT every 6 weeks. In these patients, the objective response rate was 58.3% versus 60.9% in all 184 patients treated with T-DXd. Median duration of response was 16.9 months versus 14.8 months in all patients. Median progression-free survival was 18.1 months in the patients with baseline brain metastases versus 16.4 months in all patients. For 15 of the 17 patients who had brain metastases at baseline, data was available to evaluate responses in the brain. Seven patients experienced tumour shrinkage consistent with a partial response in the brain, 7 had stable disease, and 1 had disease progression as the best response.

Based on these results, it was concluded that T-DXd shows a durable systemic disease control in patients with stable treated brain metastases at baseline, with clinical outcomes similar to those of the overall population.

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   1. Hurvitz SA, et al. Clin Cancer Res. 2019;25:2433-2441.
   2. Ogitani Y, et al. Cancer Sci. 2016;107:1039-1046.
   3. Modi S, et al. N Engl J Med. 2020;382:610-621.
   4. Jerusalem GHM, et al. Trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer with brain metastases: A subgroup analysis of the DESTINY-Breast01 trial. Abstract 526, ASCO 2021 Virtual Meeting, 4–8 June.

Want to read more? Medicom has a featured interview with Prof. Guy Jerusalem (CHU Liège, Belgium) about the DESTINY-Breast01 trial: T-DXd response on brain metastases in HER2+ breast cancer patients.

 

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Posted on 12 August 20215 July 2024