Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Letrozole

Maleic acid

Antineoplastic Agents, Immunological

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

After providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor dalpiciclib, trastuzumab and letrozole. The effectiveness of the combined treatment will be evaluated by MRI every two treatment cycles. If the disease progresses, the participant will withdraw from the trial. If the combined treatment has identified effectiveness, the participant will undergo surgical treatment within 4 weeks (over 2 weeks) after termination of the neoadjuvant treatment. The patients will be followed up for 5 years.

Pyrotinib maleate, dalpiciclib, Trastuzumab, letrozole

Nan Niu, MD

Cai-Gang Liu, PHD

NOAH study confirmed that trastuzumab combined with chemotherapy can significantly improve PCR compared with chemotherapy alone, and established the status of trastuzumab as a new adjuvant targeted therapy. The emergence of CDK4/6 inhibitors has brought hope to breast cancer patients resistant to endocrine therapy. studies have shown that pyrotinib maleate combined with CDK4/6 inhibitor can significantly inhibit the proliferation of HER2 positive breast cancer cell lines, reduce the activation of pAKT and pHER3, inhibit cell arrest in G0-G1 phase, and increase cell apoptosis. In the mouse model, pyrotinib maleate combined with CDK4/6 inhibitor exhibits higher anti-tumor activity than any anti-tumor drug alone. Moreover, the toxicity of the combined therapy does not increase compared with monotherapy. This provides a good preclinical model for the treatment of breast cancer by pyrotinib maleate combined with CDK4/6 inhibitor.

In addition, NeoALTTO study、CALGB 40601 study、NSABP B-41 study confirmed that the clinical efficacy of lapatinib combined with trastuzumab combined chemotherapy was better than that of lapatinib or trastuzumab single target treatment group. Therefore, it is envisaged that the combination of pyrotinib maleate and dalpiciclib combined with letrozole on the basis of adding new trastuzumab to treat triple positive breast cancer will further improve the curative effect.

In conclusion, we believe that pyrotinib maleate combined with trastuzumab, dalpiciclib and letrozole can provide better strategies for neoadjuvant therapy in patients with II-III three positive breast cancer.

This multi-center, single-arm, open-label trial will include 12 patients with stage II-III triple-positive breast cancer. After providing written informed consent, the participants will undergo combined treatment of pyrotinib maleate, CDK4/6 inhibitor dalpiciclib, trastuzumab，and letrozole. The effectiveness of the combined treatment will be evaluated by MRI every two treatment cycles. If the disease progresses, the participant will withdraw from the trial. If the combined treatment has identified effectiveness, the participant will undergo surgical treatment within 4 weeks (over 2 weeks) after termination of the five treatment cycles.

Pyrotinib Maleate, Trastuzumab, SHR6390 and Letrozole in Combination for Stage II-III TPBC

Pyrotinib Maleate, Trastuzumab, SHR6390(Dalpiciclib) and Letrozole in Combination for Neoadjuvant Treatment of Stage II-III TPBC

Findings from this study will indicate whether pyrotinib maleate, CDK4/6 inhibitor SHR6390 and letrozole for treatment of stage II-III triple-positive breast cancer is safe and effective

tpCR is defined as the absence of residual invasive cancer on resected breast specimen and the sampled regional lymph nodes as shown by hematoxylin-eosin staining after completion of the neoadjuvant treatment

The proportion of patients who respond to the treatment at any study time point

There was no invasive carcinoma in the primary breast lesions (ypT0-is)

RCB score is obtained according to pathological evaluation after completion of neoadjuvant treatment and surgery

It refers to the length of time from the start of treatment to the death of the patient

It refers to the length of time from the start of medication after enrollment to the death of the patient because of the recurrence, distant metastasis of the disease, invasive contralateral breast cancer, or any other cause

Number of Adverse Events using NCI CTCAE 5.0

Spots Global Cancer Trial Database for pyrotinib maleate, dalpiciclib, trastuzumab, letrozole