NCT05430347

Clinical Study of Pyrotinib in Neoadjuvant Therapy of HR-positive and HER2-positive Breast Cancer

A Multicenter Phase II Clinical Study of Pyrotinib or Pertuzumab Combined With Docetaxel, Carboplatin, and Trastuzumab in Neoadjuvant Therapy for HR-positive, HER2-positive Breast Cancer

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: The First Affiliated Hospital with Nanjing Medical University · Academic / Other
• Sex: Female
• Age: 20 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Due to neoadjuvant therapy with trastuzumab and pertuzumab is less effective for HR+/HER2+ breast cancer, and the PHEDRA Clinical Study subgroup analysis showed that the addition of pyrotinib to trastuzumab more than doubled pCR rates in HR+/HER2+ patients. our research group proposed a hypothesis that pyrotinib may be more advantageous for HR+/HER2+ breast cancer. Therefore, our center intends to carry out a multi-center, randomized controlled, prospective clinical study to compare the efficacy of pyrotinib or pertuzumab combined with docetaxel, carboplatin and trastuzumab in neoadjuvant therapy for patients with HR+/HER2+ breast cancer, and to conduct a comparative study on the safety.

Detailed description

Different anti-HER2-targeting drugs act on different parts and types of HER2 molecules, so their mechanisms and effects are different. Trastuzumab and pertuzumab are the most commonly used anti-HER2 targeting drugs, which target the extracellular segment of THE HER2 molecule. The major guidelines recommend the use of trastuzumab and pertuzumab in the use of neoadjuvant therapy with a two-target regimen. Another commonly used class of anti-HER2-targeting drugs are Tyrosine kinase inhibitors (TKI), which target the intracellular segment of the HER2 molecule. Not only that, take domestically developed pyrotinib as an example, in addition to targeting HER2, it also targets HER1 and HER4. Because of the different mechanisms of action, TKI is still effective in patients with trastuzumab and/or pertuzumab resistant relapsing metastasis. To investigate the efficacy of pyrotinib in neoadjuvant therapy, a prospective, randomized, double-blind, multicenter clinical trial, the PHEDRA Clinical Study, was conducted in China. Results presented at the 2021 ASCO Meeting showed that addition of pyrotinib to trastuzumab also significantly increased tpCR rate (22.0% vs 41.0%; P \< 0.0001), and the pCR rate was similar to trastuzumab + pertuzumab double target (39.3% for Neosphere and Peony). Based on these results, neoadjuvant therapy regimens with trastuzumab and TKI have been included in the 2022 CSCO guidelines. Of note, there were also differences in Hormone Receptor (HR) status in patients with HER2-positive breast cancer. After neoadjuvant chemotherapy combined with trastuzumab and pertuzumab double-target therapy, the pCR rate of HR-/HER2+ breast cancer was higher than HR+/HER2+ breast cancer. In contrast, a PHEDRA subgroup analysis showed that the addition of pyrotinib to trastuzumab more than doubled pCR rates in HR+/HER2+ patients (29.9% vs 12.2%) . In addition, in another adjunctive study of TKI drug neratinib, subgroup results also suggested that neratinib had a better effect on HR+/HER2+. Based on the above results, our research group proposed a hypothesis that TKI drugs may be more advantageous for HR+/HER2+ breast cancer. Therefore, our center intends to carry out a multi-center, randomized controlled, prospective clinical study to compare the efficacy of pyrotinib or pertuzumab combined with docetaxel, carboplatin and trastuzumab in neoadjuvant therapy for patients with HR+/HER2+ breast cancer, and to conduct a comparative study on the safety.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Neoadjuvant therapy: TCbHPy	Pyrotinib combined with docetaxel, carboplatin and trastuzumab (TCbHPy) for neoadjuvant therapy of HR+/HER2+ breast cancer
COMBINATION_PRODUCT	Neoadjuvant therapy: TCbHP	Pertuzumab combined with docetaxel, carboplatin and trastuzumab (TCbHP) for neoadjuvant therapy of HR+/HER2+ breast cancer

Timeline

• Start date: 2023-04-15
• Primary completion: 2025-06-15
• Completion: 2025-09-30
• First posted: 2022-06-24
• Last updated: 2023-02-21

Locations

1 site across 1 country: China