275P - Phase II study of pyrotinib plus albumin-bound paclitaxel and trastuzumab (HLX02) as neoadjuvant treatment in HER2-positive, stage II-III breast cancer

Background

The anti-HER2 targeted therapies have significantly increased the pathological complete response (pCR) of HER2-positive breast cancer (BC). We aimed to explore the efficacy of pyrotinib plus albumin-bound paclitaxel (Nab-P) and trastuzumab bioanalogue (HLX02) in neoadjuvant setting and examine the utility of serial circulating tumor cells (CTCs) testing for predicting pCR in patients with HER2-positive, stage II-III BC.

Methods

Patients with previously untreated non-metastatic HER2-positive BC were assigned to receive six neoadjuvant cycles of oral pyrotinib (400 mg) once daily, plus HLX02 (8 mg/kg loading dose, followed by 6 mg/kg) and Nab-P (260 mg/m2) q3w. The primary endpoint was pCR (ypT0/isN0). CTCs was captured and counted at baseline (P0), after neoadjuvant therapy (P1), and after surgery (P2) using Metafer-SE-iFish, and analyzed using Imaris 10.1 following image acquisition with the BZ-X800 microscope.

Results

From December 2020 to August 2023, a total of 214 patients were enrolled and completed neoadjuvant therapy and surgery. The pCR rate was 62.96% (95% CI, 55.65% -69.86%, p=. 001). The most common grade 3-4 adverse events were diarrhea (34.7%) and neutropenia (6.5%). Of 95 patients who underwent CTCs analysis, 63 (66.3%) achieved pCR. CTCs count was significantly reduced at P1 compared to that of at P0 (3.06±3.38 vs.0.84±1.53 FU/5ml, p

Conclusions

In women with HER2-positive, stage II-III BC, the neoadjuvant regimen pyrotinib plus Nab-P and HLX02 effectively promoted pCR of tumor and presented an acceptable tolerability. Personalized monitoring of CTCs during neoadjuvant therapy of early BC may aid in real-time assessment of treatment response and help predict pCR.

Clinical trial identification

NCT04917900.

Editorial acknowledgement

Legal entity responsible for the study

Ting Luo.

Funding

Beijing Science and Technology Innovation Medical Development Foundation.

Disclosure

All authors have declared no conflicts of interest.