424P - Pyrotinib plus capecitabine for trastuzumab-resistant, HER2-positive advanced breast cancer: Updated survival results from the phase II PICTURE trial

Background

Patients with HER2-positive advanced breast cancer and primary resistance to trastuzumab have a poor clinical outcome and lack good evidence to inform clinical decision. Compared with acquired resistance, primary trastuzumab resistance may have different resistance mechanisms, such as intrinsic resistance and HER2 independency. This multicenter phase 2 trial investigated the efficacy and safety of pyrotinib plus capecitabine in this population.

Methods

Patients received pyrotinib 400 mg once daily and capecitabine 1000 mg/m² twice a day on days 1-14 of each 21-day cycle until disease progression or intolerable toxicity. Based on the definitions used in prior clinical trials, primary trastuzumab resistance was defined as progression during (neo)adjuvant trastuzumab (subgroup A) or within 12 months of completing (neo)adjuvant trastuzumab (subgroup B), or progression within 6 months after initiation of first-line trastuzumab for advanced disease (subgroup C). The primary endpoint was investigator-assessed progression-free survival (PFS). This report updated survival results.

Results

Between June 20, 2019 and September 19, 2021, 100 patients were enrolled. As of April 31, 2023, the median follow-up duration was 29.7 months (95% CI, 26.9-31.5). Thirty-five deaths occurred, and the estimated median overall survival (OS) was 41.7 months (95% CI, 32.2-not reached). Subgroup B (n=49) had the longest median OS (41.7 months) and PFS (17.8 months). In patients with available data of subsequent anti-HER2 therapy after progression, 61.4%, 38.6%, and 36.4% received monoclonal antibody, tyrosine kinase inhibitor, and antibody-drug conjugate, respectively. The extended follow-up showed unchanged median PFS (11.8 months [95% CI, 8.4-15.1]) and objective response rate (70.0% [70/100]).

Conclusions

The updated OS analysis highlights the long-term efficacy of pyrotinib plus capecitabine in HER2-positive advanced breast cancer patients who have shown primary resistance to trastuzumab. Even in the era of modern anti-HER2 therapies, this clinical setting warrants more investigations to meet unmet needs.

Clinical trial identification

NCT04001621.

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.