Phase II open clinical trial to evaluate efficacy and safety of neoadjuvant trastuzumab in HER2-positive locally advanced breast cancer (LABC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 592-592
Author(s):  
C. H. Arce-Salinas ◽  
F. U. Lara ◽  
E. Leon
Keyword(s):  
Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Her2 Positive ◽  
Primary Systemic Therapy ◽  
Her 2 ◽  
Grade 3

592 Background: LABC in Mexico represents between 50–60% of the new diagnosed cases, and 25–30% of those cancers are HER-2/neu positive. Primary systemic therapy trastuzumab-based combination chemotherapy (ChT) has shown clinical benefit and pathologic complete response rates are obtained between 17%-67%. The aim of this study was evaluate the complete pathologic response (pR) rate with the combination of four cyles of FAC (5FU/Doxorubicin/Cyclophosphamide) followed by weekly paclitaxel (PTX) and trastuzumab. As secondary endpoint was evaluate cardiac safety. Methods: All patients with LABC HER-2 positive (IHC 3+ or FISH amplification) with stages IIb-IIIc were included, patients with palpable nodes underwent fine needle aspiration to confirm metastatic nodal disease (MND), other inclusion criteria was FEVI ≥55% determined by MUGA, hematologic, renal and hepatic function normal. We exclude inflammatory breast cancer. All patients received 4 cycles of FAC followed by weekly PTX (80 mg/m2) concomitantly with trastuzumab, 2 mg/kg, at the end of treatment surgery was performed, and pR was evaluable. Complete pR was defined as the absence of tumor cells in breast and axillary nodes. Disease free survival (DFS) was calculated with Kaplan-Meier method. Protocol was approved by local ethical committee. NCT 00533936. Results: We included 92 patients, median age was 48 (27–68) yrs. Median tumor size was 6 (5.4–6.5) cm, 84.9% had MND. Efficacy analysis was made in 71 patients; 21 patients are still under treatment. Overall clinical response was reached in 71% (complete 37% and partial 42%). Eleven patients were considered inoperable (skin affection, larger size > 5 cm or fixed to chest wall and received radiotherapy 50 Gy). Complete pR was reported in 48% of cases. Median follow-up was 17.4 (CI95% 14.9, 17.6) mo and media of DFS was 25.1 (CI95% 23.5, 26.7) mo. We found cardiac toxicity (CT) grade 3 in 1.1%, and grade 2 in 3.2%. Conclusions: Combination of PTX and trastuzumab after 4 cycles of FAC is highly active in terms of complete pR. This scheme was tolerated, with CT grade 3–4 in less than 2%. No significant financial relationships to disclose.

Phase II study of neoadjuvant treatment with docetaxel, capecitabine, and trastuzumab in HER-2-positive locally advanced or inflammatory breast cancer: TXH trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11581-e11581
Author(s):  
G. Perez Manga ◽  
P. Khosravi-Shahi ◽  
Y. Izarzugaza Peron ◽  
A. Soria Lovelle ◽  
R. Gonzalez del Val ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Complete Response ◽  
Conservative Surgery ◽  
End Point ◽  
Her 2

e11581 Background: Preoperative chemotherapy(CT) with trastuzumab(H)improves pathologic complete responses(pCR) in patients(ps)with Her-2+locally advanced breast cancer(LABC). Methods: This is an unicenter phaseII trial of a new neoadjuvant CT with H(without anthracyclines)in Her-2+LABC.Primary end-point was pCR.Secondary endpoints were:clinical response rate(CRR);breast conservative surgery rate(BCSR);pathologic tumoral size(pTS);disease-free survival(DFS);overall survival(OS)and toxicity profile.Ps with histologically confirmed Her-2+LABC, PS ≤2, LVEF >50%,and adequate bone marrow, renal and hepatic function were eligible.Treatment:docetaxel(T)36 mg/m2IV d1,8 and 22;capecitabine(X)750 mg/m2/12h PO d1- 14;and H 4mg/kgIV 1ºd,followed by weekly 2mg/kg in a 4-week course repeated for up to 4cycles,followed by surgery.Ps received a maximum of 6 cycles,according to investigator criteria.Radiotherapy(RT)and hormonetherapy(Ht) were allowed after surgery.Expression of markers was determined by immunohistochemistry(IHC)before CT. Results: The trial was closed due to poor accrual on March 2008.N=16ps:median age=47years(30–68); premenopausal=69%; ductal carcinoma=94%; left side=37,5%; clinical(c)stage:IIA=6.2%,IIB=43.8%;IIIA=31.2%;IIIB=18.8%;c node+=50%; median c tumoral size= 5cm(2- 10);grade:G2=53%and G3=47%;ER+ =75%;PgR+=62.5%;RP+/RE+ =62.5%;EGFR negative =87.5%;p53+=37.5;median KI67=22.5%(2- 79%);Her2+ by IHC+++ =87.5%and IHC++/FISH+ =12.5%;RT= 50%;median dose=50Gy;Ht=75%;and all ps received adjuvant H. 1º End Point: Three ps(18.8%) had pCR in breast and nodes;4ps(25%)had pCR in primary site,and among ps with c node+ 37.5%(3ps)had pCR in nodes. 2º End-Points: 1)CRR=81.2%(complete response=25%;partial=56.2%;no response=18.8%);2)BCSR=6.2%;3)Median pTS=2cm(0–5cm);4)Safety:TXH is very well tolerated:dose delays=14%;dose reductions=7%;no p had a decreased LVEF after neoadjuvant CT.Three ps had decreased LVEF during adjuvant H(median=43%).5)Only 2 events had occurred.Survival data will be reported in the meeting. Conclusions: Neoadjuvant TXH is a new active regimen in Her- 2+LABC with a manageable toxicity profile. No significant financial relationships to disclose.

Neoadjuvant dose-dense docetaxel, carboplatinum, and trastuzumab (ddTCH) chemotherapy for HER2 overexpressing breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11557-e11557 ◽  
Author(s):  
S. Bayraktar ◽  
U. D. Bayraktar ◽  
I. M. Reis ◽  
M. Pegram ◽  
C. Welsh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
High Risk Group ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Grade 3 ◽  
Dose Dense ◽  
Positive Breast Cancer

e11557 Background: Neoadjuvant chemotherapy for locally advanced breast cancer was shown to improve the complete pathologic (pCR) and clinical response (cCR) as well as the disease free survival (DFS). Docetaxel, cisplatin, and trastuzumab given every 21 days in her2-positive breast cancer demonstrated a pCR rate of 23%. The concept of dose dense chemotherapy regimens has attracted much attention and we hypothesized that dose-dense regimen would further improve pCR, cCR and would maintain the safety profile while being a suitable regimen for outpatient administration. Methods: 48 patients with stage II/III HER2-positive breast cancer were prospectively enrolled on a clinical trial of a neoadjuvant regimen consisting of docetaxel 70 mg/m2 on days 1, 15, 29, and 43; carboplatinum at an AUC of 6 on days 1, 15, 29, and 43; trastuzumab 4 mg/kg on day 1 and 2 mg/kg weekly x 10 starting on day 8; peg-filgastrim 6 mg on days 2, 16, 30, and 44. Results: The median age was 50 years (range 30–78). 52% of patients were premenopausal, 63% and 22% were of Hispanic and African descent, respectively. Estrogen receptor was positive in 52% patients and median tumor size was 5 cm at the time of diagnosis. TNM stage distribution at presentation: T1 2%, T2 25%, T3 57%, T4 16%; N0 29%, N1 46%, N2 16%, N3 7%; M0 100%. pCR in breast; axilla; and both breast and axilla was observed in 19 of 44 patients (43.2%; 95% CI 28.3% - 59.0%); in 29 of 44 patients (65.9%; 95% CI 50.1% - 79.5%); and in 16 of 44 patients (36.4%; 95% CI 22.4% - 52.2%), respectively. No grade 4 or 5 toxicity occurred. The most frequent grade 3 toxicities were hand-foot syndrome (7%), neutropenia (4%), nausea/vomiting (2%), and bone pain (2%). Grade 2 cardiotoxicity was seen in 8% of patients and no grade 3 cardiotoxicity was observed. Conclusions: This neoadjuvant regimen was well tolerated and yielded a good pCR rate for this high risk group of patients. No significant financial relationships to disclose.

Bevacizumab beginning concurrently with a sequential regimen of doxorubicin and cyclophosphamide followed by docetaxel and capecitabine as neoadjuvant therapy followed by postoperative bevacizumab alone for women with HER2-negative locally advanced breast cancer (LABC): A phase II trial of the NSABP Foundation Research Group

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 584-584
Author(s):  
P. Rastogi ◽  
M. Buyse ◽  
S. Swain ◽  
S. Jacobs ◽  
A. Robidoux ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Response ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Metastatic Breast ◽  
Complete Response ◽  
Er Positive ◽  
Grade 3 ◽  
Pathologic Complete Response Rate

584 Background: Bevacizumab with chemotherapy improves outcomes in patients with metastatic breast cancer. The purpose of this trial was to determine the activity and safety profile of bevacizumab with chemotherapy in women with LABC. Methods: Between November 2006 and August 2007, 45 women with HER-2 negative LABC initiated preoperative standard AC x 4 followed by docetaxel 75 mg/m2 IV and capecitabine 825 mg/m2 BID days 1–14 (TX) every 21 days for 4 cycles. Bevacizumab 15 mg/kg IV was given concurrently with chemotherapy every 21 days for a total of 6 preoperative doses. Postoperatively, bevacizumab was resumed for a total of 10 doses. Primary endpoint was pathologic complete response rate (pCR) in the breast. The secondary endpoints include clinical response rates and toxicity. Results: The median age was 50 yrs (range 30–78). 30 patients had stage IIIA (67%), 12 stage IIIB (27%), and 3 stage IIIC (7%) disease. Of these, 10 (22%) had inflammatory breast cancer. 27 patients (60%) had ER-positive disease. A pCR in the breast was documented in 4/44 (9%) patients, which included negative axillary nodes. A complete clinical response was noted in 14/45 (31%). One patient did not have surgery due to progression. Toxicities included hand-foot (grade 2/3–33%/22%), mucositis (grade 2/3–49%/27%), and febrile neutropenia (grade 3–24%). Conclusions: This regimen demonstrated only modest activity with substantial toxicity, and does not appear to warrant further evaluation. This clinical trial is being conducted through the support of Genentech and Roche. [Table: see text]

scholarly journals The Prognostic Impact of Body Composition for Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 608
Author(s):  
Toshiaki Iwase ◽  
Aaroh Parikh ◽  
Seyedeh S. Dibaj ◽  
Yu Shen ◽  
Tushaar Vishal Shrimanker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Composition ◽  
Adipose Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Breast

Our previous study indicated that a high amount of visceral adipose tissue was associated with poor survival outcomes in patients with early breast cancer who received neoadjuvant chemotherapy. However, inconsistency was observed in the prognostic role of body composition in breast cancer treatment outcomes. In the present study, we aimed to validate our previous research by performing a comprehensive body composition analysis in patients with a standardized clinical background. We included 198 patients with stage III breast cancer who underwent neoadjuvant chemotherapy between January 2007 and June 2015. The impact of body composition on pathologic complete response and survival outcomes was determined. Body composition measurements had no significant effect on pathologic complete response. Survival analysis showed a low ratio of total visceral adipose tissue to subcutaneous adipose tissue (V/S ratio ≤ 34) was associated with shorter overall survival. A changepoint method determined that a V/S ratio cutoff of 34 maximized the difference in overall survival. Our study indicated the prognostic effect of body composition measurements in patients with locally advanced breast cancer compared to those with early breast cancer. Further investigation will be needed to clarify the biological mechanism underlying the association of V/S ratio with prognosis in locally advanced breast cancer.

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