by Hiromichi Nakajima, Kenichi Harano, Tokiko Nakai, Shota
Kusuhara, Takehiro Nakao, Chikako Funasaka, Chihiro Kondoh, Nobuaki Matsubara,
Yoichi Naito, Ako Hosono, Shuichi Mitsunaga, Genichiro Ishii, Toru Mukohara
The Breast: Published: January 03, 2022
Highlights
•T-DXd showed favorable clinical activity against
HER2-positive metastatic breast cancer.
•T-DXd showed benefit in patients with heterogeneity,
reduction, or loss of HER2 expression.
•Patients with liver metastasis tended to have worse
outcomes.
Abstract
Background
The previous second-line treatment for HER2-positive
metastatic breast cancer were ado-trastuzumab emtansine (T-DM1); however, its
activity is decreased in tumors with heterogenous, reduced, or loss of HER2
expression. Trastuzumab deruxtecan (T-DXd) has recently been developed as a
novel antibody-drug conjugate to overcome resistance to T-DM1. However,
clinical evidence on its ability to overcome this resistance is limited.
Materials and methods
We retrospectively analyzed data for patients with
HER2-positive metastatic breast cancer who received T-DXd at our institution
from April 2020 to March 2021. We evaluated the associations between
clinicopathological and molecular biomarkers and the efficacy of T-DXd.
Results
Twenty-two patients were enrolled in this study. The median
progression-free survival (PFS) was 9.7 months (95% confidence interval [CI],
7.0–not reached [NR]), and the objective response rate (ORR) was 61.9%. The ORR
and PFS were comparable between patients with HER2 immunohistochemistry scores
of 3+ and 2+/1+ at initial diagnosis (ORR: 50.0% vs. 72.7%, p = 0.39;
median PFS, 9.7 months [95%CI, 2.6–NR] vs. 8.3 months [95%CI, 7.1–NR]; hazard
ratio, 1.86 [95%CI, 0.53–6.57], p = 0.34). Two patients with
heterogenous HER2 expression had a partial response or long stable disease (≥6
months). Three of four patients with re-biopsy samples after anti-HER2 targeted
therapy and with latest HER2 immunohistochemistry scores of 1+ experienced
partial responses (75.0%) to T-DXd, but none had responded to prior T-DM1.
Conclusions
T-DXd demonstrated favorable activity in clinical practice.
Moreover, T-DXd showed meaningful benefit in patients with heterogeneity,
reduction, or loss of HER2 expression.
