406TiP - Phase II trial of primary systemic therapy (PST) with docetaxel (D) followed by high-dose epirubicin in combination with cyclophosphamide (EC) plus...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Locally Advanced
Presenter Patrizia Vici
Authors P. Vici1, L. Pizzuti2, M. Mottolese3, D. Sergi2, A. Di Benedetto3, C. Botti4, L. Perracchio5, E. Pescarmona5, A. Carpino6, L. Di Lauro7
  • 1Division Of Medical Oncology B, Regina Elena National Cancer Institute, 00144 - Rome/IT
  • 2Division Of Medical Oncology B, Regina Elena National Cancer Institute, Rome/IT
  • 3Molecular Medicine Department, Regina Elena National Cancer Institute, Rome/IT
  • 4A Surgery Division, Regina Elena National Cancer Institute, Rome/IT
  • 5Pathology Department, Regina Elena National Cancer Institute, Rome/IT
  • 6Cardiology Division, Regina Elena National Cancer Institute, Rome/IT
  • 7Medical Oncology B, Regina Elena National Cancer Institute, Rome/IT

Abstract

Background

PST with taxanes, anthracycline-containing regimens and T showed a high percentage of pathologic complete response (pCR); T administered concurrently with chemotherapy is more effective, but the combination with anthracyclines may be at risk of cardiotoxicity. The present study evaluates efficacy and toxicity of T administered concurrently with a sequential regimen of D followed by EC in neoadjuvant setting.

Materials and methods

This phase II single stage trial is enrolling pts with cT2-T4, N0-2, M0, Her-2 positive (IHC 3+ or 2+ amplified) breast cancer. A core biopsy is required prior treatment start to evaluate hormonal receptors, Ki67, topoisomerase II, Her-2, with re-evaluation of these parameters, whenever possible, at definite surgery. LVEF is evaluated before and during treatment. Blood samples are collected at baseline for evaluation of 9 genetic polymorphisms related to higher risk of developing cardiac toxicity. We are quantitatively evaluating gene copy number by multiple ligand probe amplification (MLPA), PTEN, p-Akt, p-MAPK, and PIK3CA mutations. Pts receive 4 cycles of D (100mg/m2) plus T (loading dose 8mg/kg followed by 6mg/kg), followed by 4 cycles of EC (120/600mg/m2) plus T, every 3 weeks. Definite surgery is planned at the end of PST, and standard radiotherapy and hormonal adjuvant treatment in case of positive hormonal receptors are given; adjuvant T is given for 6 months. The primary objective of the trial is pCR (absence of invasive tumor cells in the breast and axilla); secondary objectives are cardiac safety, toxicity, disease-free survival. The planned sample size is 42 pts.

Results

To date, 29 pts have been enrolled; median age is 45 years, pre/postmenopausal 22/7, ER and/or PgR positive in 16 pts. 27 pts are evaluable for pathological response: we observed 20 pCR (74%, 95%C.I, 57.5-90.6). Grade 3-4 neutropenia was the most frequent toxicity, encountered in 75% of the pts, other toxicities were mild to moderate. No clinical cardiotoxicity was observed.

Conclusions

At preliminary analysis, PST with sequential administration of D followed by EC, given concurrently with T, appears to be very active and safe in stage II-III breast cancer pts.

Disclosure

All authors have declared no conflicts of interest.