LBA19 - Pyrotinib or placebo in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer (PHILA): A randomized phase III trial

Background

Pyrotinib (pyro, an irreversible pan-HER inhibitor) plus capecitabine has demonstrated antitumor activity as 2L treatment in HER2-positive metastatic breast cancer (mBC) (Lancet Oncol 2021). Pertuzumab combined with trastuzumab (H) and docetaxel (T) is the standard 1L dual anti-HER2 therapy for HER2-positive mBC. Here, we report the efficacy and safety of dual anti-HER2 regimen of Pyro+H+T (PyroHT) compared with placebo+H+T (HT) in untreated HER2-positive mBC.

Methods

Eligible pts were randomized (1:1) to receive oral Pyro (400 mg QD) or placebo, both combined with intravenous H (8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles) and T (75 mg/m²) on day 1 of each 21-day cycle. The primary endpoint was PFS per investigator (INV). Data cutoff for this prespecified interim analysis was May 25, 2022.

Results

Between May 2019 and Jan 2022, 590 eligible pts from 40 centers were randomized and treated (297 with PyroHT and 293 with HT). Median follow-up was 15.8 mo and 14.9 mo, respectively. PFS per INV of PyroHT was significantly longer than HT (median, 24.3 mo [95% CI 19.1-33.0] vs 10.4 mo [95% CI 9.3-12.3]; HR, 0.41 [95% CI 0.32-0.53]; P < 0.0001; subgroup results are in Table 1), which was consistent with PFS per IRC (median, 33.0 vs 10.4 mo; HR, 0.35 [95% CI 0.27-0.46]). The most common grade ≥3 TRAEs were decreased neutrophil count (62.6% vs 65.2%), decreased WBC count (53.2% vs 50.9%), and diarrhea (46.5% vs 3.1%). Grade 3 diarrhea occurred mainly during cycle 1 and substantially decreased in cycle 2 and thereafter. No grade 4 or 5 diarrheas occurred. Serious TRAEs occurred in 24.9% vs 6.1% of pts and treatment-related deaths occurred in 0 vs 0.3% of pts, respectively. Table: LBA19

Subgroup analyses of PFS per INV

n/N=events/patients. HRs are from unstratified analyses.

Conclusions

PyroHT significantly prolonged PFS over HT in pts with HER2-positive mBC. The safety is manageable. To our knowledge, this is the second phase 3 trial to demonstrate PFS benefit from dual HER2 inhibition in 1L treatment of HER2-positive mBC.

Clinical trial identification

NCT03863223.

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

B. Xu: Non-Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer, Roche, Eisai; Financial Interests, Personal, Advisory Role: Roche.. F. Dong: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd. S. Wu: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd. X. Zhu: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd. All other authors have declared no conflicts of interest.