445P - Tyrosine kinase inhibitors (TKIs) in HER2-positive metastatic breast cancer after trastuzumab emtansine (T-DM1) failure: A multicenter real-world study

Background

Trastuzumab emtansine (T-DM1) is recommended as the standard treatment of second-line therapy of HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab. However, subsequent therapeutics after T-DM1 failure remain controversial. This study investigated the effectiveness and safety of tyrosine kinase inhibitors (TKIs)-based therapy in HER2-positive MBC with T-DM1 resistance.

Methods

From September 2018 to October 2021, 53 patients with HER2-positive MBC who received TKIs-based therapy after T-DM1 failure were enrolled in this multicenter real-world study. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), clinical benefit rate (CBR) and safety.

Results

53 patients received TKIs-based therapy in 2 or later line treatment. The median PFS of TKIs-based therapy was 11.9 months (95% CI 7.9-15.9). ORR and CBR were 19.6% and 72.5%, respectively. A median PFS of 10.5 months (95% CI 7.5-13.5) and an intracranial ORR of 33.3% were observed among patients with brain metastasis (n=12). A better PFS was observed among patients with pyrotinib (n=21) compared with lapatinib (n=30), and patients who derived favorable benefit from T-DM1 (PFS ≥ 6 months). Hormone receptor status (HR) and T-DM1 response were independent indicators for curative effect of TKIs-based therapy. The most commonly adverse events were thrombocytopenia (23.6%), diarrhea (15.7%), leucopenia (15.7%), and hand-foot syndrome (15.7%).

Conclusions

TKIs-based therapy showed promising efficacy and safety in patients with HER2-positive MBC after T-DM1 failure, including those with brain metastases. Patients who benefited from prior T-DM1 achieved a significantly longer PFS in subsequent TKIs-based therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Province Hospital.

Funding

Y. Yin.

Disclosure

All authors have declared no conflicts of interest.