Neoadjuvant Treatment With Trastuzumab in HER2-Positive Breast Cancer: Results From the GeparQuattro Study

Abstract

PURPOSE Trastuzumab, a humanized antibody against the human epidermal growth factor receptor type 2 (HER2), has shown high efficacy in breast cancer. We prospectively investigated its efficacy given simultaneously with anthracycline-taxane-based neoadjuvant chemotherapy. PATIENTS AND METHODS Patients with operable or locally advanced, HER2-positive tumors were treated preoperatively with four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel with or without capecitabine (EC-T[X]) and trastuzumab 6 mg/kg (with a loading dose of 8 mg/kg) every 3 weeks during all chemotherapy cycles. Patients with HER2-negative tumors treated in the same study with the same chemotherapy but without trastuzumab were used as a reference group. Results Of 1,509 participants, 445 had HER2-positive tumors treated with trastuzumab and chemotherapy. Pathologic complete response (pCR; defined as no invasive or in situ residual tumors in the breast) rate was 31.7%, which was 16% higher than that in the reference group (15.7%). HER2-positive patients without response to the first four cycles of EC showed an unexpectedly high pCR rate of 16.6% (3.3% in the reference group). Breast conservation rate was 63.1% and comparable to that of the reference group (64.7%). EC-T(X) plus trastuzumab was associated with more febrile neutropenia and conjunctivitis, but with a comparable short-term cardiac toxicity profile as the reference group. CONCLUSION This trial confirms that combining trastuzumab with anthracycline-taxane-based neoadjuvant chemotherapy results in a high pCR rate without clinically relevant early toxicity. Combination of chemotherapy with trastuzumab should be considered when neoadjuvant treatment is given to patients with HER2-positive breast cancer.

Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials

“…Between 1998 and 2006, a total of eight major prospective neoadjuvant trials in 6625 breast cancer patients were conducted in Germany [9,10,11,12,13,14,15,16,17,18]. Details of design and conduct of individual trial were previously reported (Table 1).…”

“…Details of design and conduct of individual trial were previously reported (Table 1). Seven trials were phase III randomized parallel-group trials (6408 patients) [9][10][11][12][13][14][15][16][17] and one was a phase II case series (217 patients) [18] In the GeparTrio main trial [12,13], the 622 non-responders were randomized to 4 further cycles of TAC (321 patients) or 4 cycles of NX (301 patients), whereas the 1390 responders were allocated to 4 or 6 further cycles of TAC (704 and 686 patients, respectively). To avoid confounding by treatment selection according to intermediate clinical assessment of tumor response, we excluded the 334 patients allocated to NX, a proportional random sample of 95 responders, who received a total of 6 cycles of TAC in the GeparTrio pilot trial [11], and the 686 responders, who received a total of 8 cycles of TAC in the GeparTrio main trial [12,13].…”

“…To avoid confounding by treatment selection according to intermediate clinical assessment of tumor response, we excluded the 334 patients allocated to NX, a proportional random sample of 95 responders, who received a total of 6 cycles of TAC in the GeparTrio pilot trial [11], and the 686 responders, who received a total of 8 cycles of TAC in the GeparTrio main trial [12,13]. 134 patients included in the run-in period of GeparTrio [12,13] and GeparQuattro [14,15] who dropped out before randomization because of progression, malcompliance, or side-effects, were analyzed in actual treatment arms as determined by computer-generated random allocation. Characterization of tumor subtypes by human epidermal growth factor receptor 2 (HER2) was not protocol mandated in the early trials.…”

Semiquantitative hormone receptor level influences response to trastuzumab-containing neoadjuvant chemotherapy in HER2-positive breast cancer

“…9,11,13 This is because trastuzumab has been only rarely used in neoadjuvant chemotherapy regimens before 2006, where its use was limited to clinical trials (MD Anderson trial, NOAH trial and GeparQuattro trial). [14][15][16] Recently, trastuzumab is increasingly used preoperatively in HER2 þ breast carcinoma, often as TCH regimen (Taxoteres, carboplatinum, Herceptins) or as AC followed by TH (ie, adriamycin, cyclophosphamide followed by taxane and herceptin) or in some other combination. 17,18 Pathologic complete response to neoadjuvant chemotherapy without trastuzumab in hormone receptor-negative/HER2 þ tumors is seen in 27-45% of cases.…”

“…9 It is speculated and also shown in recently concluded clinical trials that addition of trastuzumab to neoadjuvant chemotherapy regimen will increase the pathologic complete response rates in all HER2 þ tumors. [14][15][16]19 However, even in these clinical trials the effect of trastuzumab on different subsets of HER2 þ tumors has not been addressed. The primary aim of this study was to analyze the rate of pathologic complete response in different types of HER2 þ tumors.…”