Background:
HER2-positive breast cancer is known to carry an adverse prognosis compared to HER2-negative disease, which may however be compensated by the use of HER2-targeted agents. Therefore, most patients with HER2-positive disease larger than 5 mm receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline containing regimes. Previous investigations on neoadjuvant treatment with TCH showed pCR-rates in the range of 40%, however, survival data have not yet been presented. Here we present 4-year follow-up data for a cohort of 51 patients treated with neoadjuvant TCH.
Methods:
We treated 51 patients with operable HER2-positive breast cancer with a neoadjuvant schedule of docetaxel (75 mg/m2) and carboplatin (AUC 6) q3w and trastuzumab (2(4)mg/kg) q1w. Lymph node involvement was verified by SLNB or core-cut-biopsy. Patients were diagnosed at a mean age of 55 years, 68.6% had ER positive tumors, 39.2% presented with grade 3 disease and 49% of patients were node-positive. Patients were monitored every two cycles by ultrasound. After 6 cycles of chemotherapy all patients had surgery. Axillary dissection was performed in case of positive lymph node status prior to TCH. After surgery trastuzumab was continued q3w up to one year.
Results:
In 50 patients TCH could be administered as planned without dose reductions or delays. One patient suffered from an allergic reaction on taxane after the second cycle, resulting in replacement by gemcitabine. Side effects were mild, no grade III/IV toxicities occurred and no case of cardiomyopathia was observed. 21 (41.18%) patients achieved a pCR, 18 (72.0%) patients converted from cN+ to ypN0. Outcome data at a median follow-up of 51.6 months are as follows.
All patients (n=51)pCR (n=21)N+ (n=25)cN+ → ypN0 (n=18)ER positive (n=35)G3 (n=20)DFS (n/%)42/82.3517/80.9517/68.016/88.8931/88.5716/80.0DDFS (n/%)46/90.219/90.4820/80.017/94.4433/94.2918/90.0OS (n/%)48/94.1821/100.022/88.018/100.034/97.1419/95.0
Conclusion:
Outcome following neoadjuvant TCH as observed in our analysis compares well to outcome data observed in adjuvant trastuzumab trials such as HERA (4-year follow-up; DFS 78.6% and OS 89.3%) or BCIRG006 (36-month follow-up; DFS 82% and OS 91% in the TCH-arm). Particularly among patients with ER positive disease and those experiencing axillary conversion we obseverd an excellent outcome. Importantly, TCH was well tolerated in our cohort. Therefore our data support the use of TCH as neoadjuvant therapy regimen for patients with HER-positive breast cancer. They also strongly encourage the use of docetaxel and carboplatin as chemotherapy backbone in studies investigating the dual blockade with trastuzumab and pertuzumab in the neoadjuvant setting.
Citation Format: Kolberg H-C, Akpolat-Basci L, Stephanou M, Hannig CV, Liedtke C. Neoadjuvant chemotherapy with docetaxel, carboplatin and weekly trastuzumab (TCH) is active in HER2-positive early breast cancer: Results after a median follow-up of over 4 years. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-14-06.
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