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. 2022 Dec 2;12(12):2754-2762.
doi: 10.1158/2159-8290.CD-22-0837.

Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis

Guy Jerusalem  1 , Yeon Hee Park  2 , Toshinari Yamashita  3 , Sara A Hurvitz  4 , Shanu Modi  5 , Fabrice Andre  6 , Ian E Krop  7 , Xavier Gonzàlez Farré  8 , Benoit You  9 , Cristina Saura  10 , Sung-Bae Kim  11 , Cynthia R Osborne  12   13 , Rashmi K Murthy  14 , Lorenzo Gianni  15 , Toshimi Takano  16 , Yali Liu  17 , Jillian Cathcart  17 , Caleb Lee  17 , Christophe Perrin  18
Affiliations

Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis

Guy Jerusalem et al. Cancer Discov. .

Abstract

DESTINY-Breast01 (NCT03248492) evaluated trastuzumab deruxtecan (T-DXd; DS-8201) in patients with heavily pretreated HER2-positive metastatic breast cancer (mBC). We present a subgroup of 24 patients with a history of treated brain metastases (BM), a population with limited treatment options. In patients with BMs, the confirmed objective response rate (cORR) was 58.3% [95% confidence interval (CI), 36.6%-77.9%], and the median progression-free survival (mPFS) was 18.1 months (95% CI, 6.7-18.1 months). In patients without BMs (n = 160), cORR was 61.3% and mPFS was 16.4 months. Eight patients (47.1%) experienced a best overall intracranial response of partial response or complete response. Seven patients (41.2%) had a best percentage change in brain lesion diameter from baseline consistent with stable disease. Two patients (8.3%) with BMs and two (1.3%) without BMs experienced progression in the brain. The safety profile of T-DXd was consistent with previous studies. The durable clinical activity of T-DXd in this population warrants further investigation.

Significance: Advances in treating HER2-positive metastatic breast cancer have greatly improved patient outcomes, but intracranial progression remains an important risk for which few therapeutic options are currently available. T-DXd demonstrated durable efficacy in patients with stable, treated BMs. This article is highlighted in the In This Issue feature, p. 2711.

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Figures

Figure 1. PFS. Kaplan–Meier analyses in the BM and non-BM subgroups. The tick marks in each panel indicate patient data that were censored.
Figure 1.
PFS. Kaplan–Meier analyses in the BM and non-BM subgroups. The tick marks in each panel indicate patient data that were censored.
Figure 2. Central nervous system response. A, Best response in brain lesions in patients with stable BMs in the BM subgroup. B, Brain lesion measurements over time in patients with stable BMs in the BM subgroup. Three patients with reported baseline measurements had no change over time. Two patients with brain metastases at baseline did not have sufficient data to evaluate response in the brain and are not shown.
Figure 2.
CNS response. A, Best response in brain lesions in patients with stable BMs in the BM subgroup. B, Brain lesion measurements over time in patients with stable BMs in the BM subgroup. Three patients with reported baseline measurements had no change over time. Two patients with BMs at baseline did not have sufficient data to evaluate response in the brain and are not shown.
See this image and copyright information in PMC

References

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