414P - Trastuzumab deruxtecan for HER2-positive breast cancer brain metastasis: A systematic review and meta-analysis

Background

Brain metastases (BMs) affect approximately half of the patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and holds a poor prognosis. Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate, has shown promising results in patients with breast cancer brain metastases (BCBMs). Thus, we conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of T-DXd in the HER2-positive BCBM population.

Methods

We searched PubMed, Embase, and Cochrane Library databases, as well as ASCO, ESMO, and SABCS websites for clinical trials (CTs) and observational studies evaluating T-DXd in the HER2-positive BCBM patients. Heterogeneity was assessed with the Cochran Q test and I2 statistics. Random effects models were used for all statistical analyses, which were performed using R software (v.4.2.2).

Results

Ten studies were included, six clinical trials (N=189) and four observational studies (N=147), with a total of 336 patients. The mean progression-free survival was 15 months (95% CI 13.9 to 16.1 months). The objective response rate (ORR) was 61% (95% CI 53-68%), and the intracranial (IC)-ORR was 62% (95% CI 55-70%). No significant differences in ORR and IC-ORR were observed between CTs and observational studies (p=0.56, and p=0.46, respectively). The clinical benefit rate (CBR) was 86% (95% CI 72-94%), and the IC-CBR was 69% (95% CI 59-79%). The ORR was 64% (95% CI 53-73%) in the subgroup of patients with stable BMs and 61% (95% CI 49-73%) in patients with active BMs, with no significant difference between groups (p=0.78). Adverse events (AE) of any grade were reported in 98% of cases (95% CI 90-100%). Dose reduction and drug interruption due to AE were reported in 29% (95% CI 10-60%) and 31% (95% CI 19-42%) of cases, respectively.

Conclusions

Our systematic review and meta-analysis supports the intracranial activity of T-DXd in both patients with stable BM and active BM. HER2-positive BCBM patients treated with T-DXd achieved ORR and IC-ORR higher than 50% in the clinical trials setting and in real-world data.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.