382P - Pyrotinib combined with metronomic oral etoposide (VP-16) in heavily pretreated HER2-positive metastatic breast cancer: A single-arm, phase II study

Background

Exploration of anti-HER2 combination regimens in the later-line treatment for heavily pretreated HER2-positive metastatic breast cancer (MBC) and how to improve survival benefits and compliance are still urgent in clinical practice. Currently, optimal third- and later-line treatment standards are still not established yet, and multiple approaches have been used, including combinations based on chemotherapies, monoclonal antibodies, or both with oral anti-HER2 tyrosine kinase inhibitors (TKIs). The current single-arm prospective phase II study aimed to evaluate the efficacy and safety of pyrotinib in combination with metronomic oral etoposide in heavily pretreated HER2-positive MBC.

Methods

Eligible HER2-positive MBC patients previously treated with trastuzumab were enrolled to receive oral pyrotinib 400mg per day and metronomic oral etoposide 50mg per day d1-21 every 28 days, until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR, CR + PR + SD ≥6 months), overall survival (OS), and safety.

Results

From November 2018 to March 2022, 22 eligible patients were enrolled, with a median of 4 prior treatment regimens for MBC. Among the 20 evaluable patients, 6 patients (30.0%) achieved PR, 10 patients (50.0%) achieved SD, and 4 patients (20.0%) reached PD. The ORR was 30% (6/20), the DCR was 80% (16/20), and the CBR was 65.0%. During the follow-up of 20 evaluable patients up to August 2023, the median PFS was 9.0 months (95% CI, 7.6-10.4 months), and the median OS was 27.0 months (95%CI, 20.9-33.1 months). The most common grade 3 adverse events (AEs) included nausea (15%), vomiting (15%), diarrhea (5%), anemia (5%), and peripheral neuropathy (5%). No grade 4 or lethal AEs were observed.

Conclusions

The combination of pyrotinib with metronomic oral etoposide has achieved promising clinical benefits in heavily pretreated HER2-positive MBC, with acceptable and manageable toxicity. Our findings provide an alternative treatment option for the later-line treatment of HER-positive MBC, which worth further investigation.

Clinical trial identification

NCT03923179.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

CAMS Innovation Fund for Medical Sciences (CIFMS).

Disclosure

All authors have declared no conflicts of interest.