Trastuzumab emtansine vs lapatinib and capecitabine in HER2-positive metastatic breast cancer brain metastases: A real-world study

by Thibaut Sanglier, Jinjoo Shim, Neil Lamarre, Claudia Peña-Murillo, Vincent Antao, Filippo Montemurro 

The Breast: Published: January 15, 2023

Background

Trastuzumab emtansine (T-DM1) has demonstrated improvements in survival and neurological symptoms in patients with breast cancer with brain metastases (BCBM). This real-world study investigated the effectiveness of T-DM1 versus lapatinib plus capecitabine (LC) in patients with BCBM.

Methods

This retrospective, observational study evaluated patients with HER2–positive BCBM using a real-world database. Eligible patients had initiated T-DM1 or LC with a prior diagnosis of brain metastasis and ≥1 prior metastatic breast cancer treatment. The primary endpoint was overall survival (OS); secondary endpoints were time to next relevant treatment or death (TTNT) and real-world progression-free survival (rwPFS). An inverse probability of treatment weighting (IPTW) approach was used to account for differences in potential baseline characteristics between treatment groups. Outcomes were described using the Kaplan-Meier method, and the average treatment effect of initiating T-DM1 versus LC was estimated using weighted Cox proportional hazard models and hazard ratio (HR).

Results

A total of 214 patients were available for analysis (T-DM1, n = 161; LC, n = 53). Demographics and baseline characteristics were generally well-balanced between treatment groups after weighting. After weighting, median OS was 17.7 (T-DM1) versus 9.6 (LC) months (HR, 0.55 [95% CI, 0.34–0.89]; P=0.013). Median TTNT was 9.0 (T-DM1) versus 6.0 (LC) months (HR, 0.55 [95% CI, 0.36–0.85]; P = 0.005). After weighting, median rwPFS was 6.0 (T-DM1) versus 4.0 (LC) months (HR, 0.50 [95% CI, 0.36–0.69]; P < 0.001).

Conclusions

These results support the superior effectiveness and clinical relevance of T-DM1 versus LC in patients with HER2-positive BCBM in the real world.

Breast Surgery Bulletin - January 2022

 

Impacts of clinicopathological factors on efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer

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.