Although neoadjuvant dual anti-HER2-targeted therapy, pertuzumab and trastuzumab, combined with taxanes increased the pCR rate for patients with early-stage HER2-positive breast cancer when compared with single blockade combined with chemotherapy, certain patients did not achieve pCR after receiving dual blockade or single blockade targeting HER2 combined with taxanes.
Based on the cardiac safety and promising ORR rate of the regimens consisting of PLD and cyclophosphamide and trastuzumab in treating patients with HER2-positive breast cancer in the neoadjuvant or metastatic setting, the investigators hypothesized that dual blockades targeting HER2, trastuzumab and pertuzumab, combined with PLD and cyclophosphamide, will not only increase the pCR rate but also cause less cardiotoxicity for participants with residual cancer via core biopsy or non-clinical CR after receiving taxanes plus trastuzumab and pertuzumab or taxanes plus trastuzumab. The investigators also showed that ctDNA served as the surrogate prognostic marker for participants with HER2-positive EBC who received neoadjuvant trastuzumab-based regimens.
In this study, the investigators will explore whether the combination of PLD (Lipo-Dox®, Liposomal Doxorubicin Injection), cyclophosphamide, trastuzumab, and pertuzumab can increase the pCR rate of participants with HER2-positive EBC if they have residual cancers (core biopsy, non-clinical CR, or positive ctDNA) after receiving a trastuzumab and taxanes-based NAT regimen. In addition, the cardiac safety, adverse effects, and clearance of ctDNA will be explored for these patients. The investigators further assess the feasibility of VAB (before operation) in these participants who achieved negative ctDNA after receiving Lipo-Dox® plus cyclophosphamide, trastuzumab, and pertuzumab.
Histologically confirmed invasive breast carcinoma
HER2-positive breast carcinoma
HER2-positive status will be based on pretreatment biopsy material and defined as an immunohistochemistry (IHC) score of 3+ and/or positive by fluorescence in situ hybridization (FISH) prospectively confirmed by a pathology laboratory before study enrollment.
FISH positivity is defined as a ratio of ≥ 2.0 for the number of HER2 gene copies to the number of signals for chromosome 17 copies.
Stage IV (metastatic) breast cancer.
History of any prior (ipsilateral- or contralateral) breast cancer except lobular carcinoma in situ.
History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ (CIS) of the cervix, non-melanoma skin carcinoma, stage I uterine cancer, or other non-breast malignancies with an outcome similar to those mentioned above.
Patients for whom radiotherapy would be recommended for breast cancer treatment, but for whom it is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation).
Single group
Lipo-Dox®
DrugLipo-Dox®: 37.5 mg/m² on D1; every 21 days is one cycle, for a total of 4 cycles.
Cyclophosphamide
DrugCyclophosphamide 600 mg/m² on D1, ; every 21 days is one cycle, for a total of 4 cycles.
Trastuzumab (Herceptin)
DrugTrastuzumab 6 mg/kg on D2; every 21 days is one cycle, for a total of 4 cycles.
Pertuzumab
DrugPertuzumab 420 mg on D2; every 21 days is one cycle, for a total of 4 cycles.
Pathological complete remission rate (pCR)
Assessment of pathological specimens to determine when no cancer cells are detected in tissue samples (breast and lymph nodes) removed during surgery following preoperative treatment, such as chemotherapy.
Number of participants with Lipodox-containing regimen-related adverse events of cardiac function as assessed by CTCAE v4.0
Cardiac echo to assess the left ventricle ejection fractions before and after completion of Lipo-Dox®-containing regimen
Clearance rate of circulating tumor DNA [ctDNA]
Circulating tumor DNA (ctDNA) clearance refers to the transition from a detectable level of tumor-specific mutations in the bloodstream to undetectable levels following neoadjuvant treatment, including TH or THP regimen, or Lipodox plus cyclophosphamide, trastuzumab, and pertuzumab.
Number of participants with treatment with Lipo-Dox®-containing regimen-related adverse events as assessed by CTCAE v4.0.
Adverse events of Lipodox plus cyclophosphamide, trastuzumab, and pertuzumab.
Percentage of patients with complete removal of lesion via vacuum-assisted biopsy
Comparison of the percentage of patients with a lack of pathology at the surgery between vacuum-assisted biopsy and surgical operation (ctDNAs are negative after completion of neoadjuvant chemotherapy).
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National Taiwan University Hospital
Lead sponsor
TTY Biopharm
Collaborator
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