447P - Efficacy and safety of trastuzumab with or without a tyrosine kinase inhibitor for HER2-positive breast cancer: A systematic review and meta-analysis

Background

This study aimed to explore whether the combination of trastuzumab and small molecule tyrosine kinase inhibitor (TKI) can further improve the efficacy of HER2-positive breast cancer without adding additional adverse events.

Methods

PubMed, Embase, Cochrane, and Web of Science were systematically searched for relevant articles from inception until Nov 2022. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes. Subgroup analyses were performed based on disease status and TKI types.

Results

A total of 10,623 patients from 16 studies were included in this meta-analysis. Trastuzumab combined with TKI dual-target blockade showed significant improvement in PFS and OS compared with trastuzumab single-targeted therapy. A random-effects model was applied and the pooled HR was 0.52 (95% CI: 0.41–0.66, P<0.001), suggesting that trastuzumab plus TKI was highly associated with better PFS. Further subgroup analysis of the different TKI agents (including lapatinib, pyrotinib, and tucatinib) showed that combination therapy was related to better PFS in all subgroups. In the metastatic setting, patients receiving trastuzumab combined with TKI had significantly longer OS than those receiving trastuzumab monotherapy (HR=0.71, 95% CI: 0.58–0.87, P=0.001). Besides, higher objective response rate was observed with trastuzumab plus TKI (OR=2.17, 95% CI: 1.34–3.50, P=0.002). Patients receiving combination therapy had a higher incidence of discontinuation, and grade ≥3 diarrhea.

Table: 447P

Subgroup analysis for the OS and PFS

Conclusions

In summary, combining TKI with trastuzumab confers a significant improvement in clinical outcomes with tolerable toxicity for individuals with HER2-positive breast cancer, especially in advanced settings. The different efficacies of TKIs combined with trastuzumab may be related to the mechanism of action of the different TKIs.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

L. Li.

Funding

National Key Research and Development Program of China (2021YFF1201300); CAMS Innovation Fund for Medical Sciences (2021-I2M-1-014); Medical Oncology Key Foundation of Cancer Hospital Chinese Academy of Medical Sciences (CICAMS-MOCP2022007); Cultivation project of Medical Oncology Key Foundation of Cancer Hospital Chinese Academy of Medical Sciences (CICAMS-MOCP2022007).

Disclosure

All authors have declared no conflicts of interest.