De-escalation of Neoadjuvant Treatment (Paclitaxel + HP) in Early HER2+ Breast Cancer

This phase II study evaluates the efficacy and safety of a de-escalated neoadjuvant chemotherapy regimen in patients with early-stage HER2-positive breast cancer. The experimental regimen consists of 12 weekly cycles of paclitaxel combined with trastuzumab and pertuzumab (THP), without anthracyclines. The study aims to determine if this less toxic regimen can achieve high rates of pathological complete response (pCR) comparable to standard anthracycline-containing regimens. The results are compared with a historical control group of patients who received the standard TCHP regimen (docetaxel, carboplatin, trastuzumab, pertuzumab). A total of 186 participants are included in the analysis: 93 patients prospectively treated with the de-escalated THP regimen and 93 patients in the retrospective historical control group (TCHP). The primary endpoint is the pCR rate at the time of surgery. Secondary endpoints include toxicity, rate of breast-conserving surgery, and 3-year event-free survival.

Sex

Female

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

* Histologically confirmed invasive breast carcinoma.
* HER2-positive status defined as IHC 3+ or FISH amplification (ratio \>= 2.0).
* Clinical Stage IIA-IIB (cT1-T2 N0-N1, cT3 N0, M0).
* Operable disease planned for surgical resection.
* ECOG performance status 0-1.
* Left Ventricular Ejection Fraction (LVEF) \>= 50% by Echocardiography.
* Adequate bone marrow, hepatic, and renal function.
* Signed informed consent form.

Exclusion Criteria:

* Metastatic disease (Stage IV).
* Prior systemic therapy for breast cancer (chemotherapy, immunotherapy, or anti-HER2 therapy).
* Serious cardiac history (congestive heart failure, unstable angina, myocardial infarction within 6 months).
* Other synchronous or metachronous malignancies within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix).
* Pregnancy or breastfeeding.
* Known hypersensitivity to study drugs.

• BACKGROUNDNitz UA, Gluz O, Christgen M, Grischke EM, Augustin D, Kuemmel S, Braun M, Potenberg J, Kohls A, Krauss K, Stefek A, Schumacher C, Forstbauer H, Reimer T, Fischer H, Liedtke C, Wuerstlein R, Schumacher J, Kates R, Kreipe H, Harbeck N. De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab +/- weekly paclitaxel. Ann Oncol. 2017 Nov 1;28(11):2768-2772. doi: 10.1093/annonc/mdx494. PMID 28945833
• BACKGROUNDWaks AG, Desai NV, Li T, Poorvu PD, Partridge AH, Sinclair N, Spring LM, Faggen M, Constantine M, Metzger O, Alberti J, Deane J, Rosenberg SM, Frank E, Tolaney SM, Krop IE, Tung NM, Tayob N, King TA, Mittendorf EA, Winer EP. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022 May 10;8(1):63. doi: 10.1038/s41523-022-00429-7. PMID 35538105
• BACKGROUNDSchneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortes J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. doi: 10.1093/annonc/mdt182. Epub 2013 May 22. PMID 23704196