Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

Safety and efficacy of capecitabine (C) plus bevacizumab (B) as first-line in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1013-1013 ◽  
Author(s):  
G. Sledge ◽  
K. Miller ◽  
C. Moisa ◽  
W. Gradishar
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Objective ◽  
First Line ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Grade 3

1013 Background: C alone has good activity and tolerability in metastatic breast cancer (MBC) and when combined with docetaxel improves response and survival. C combined with B in heavily pretreated MBC improved the response rate but not PFS. In untreated MBC, the addition of B to chemotherapy significantly improves progression-free survival (PFS) which suggests that B, is most effective in early disease. Methods: Primary objective of this single-arm, 2-phase study, is to evaluate PFS in MBC patients receiving first-line treatment with C 1,000 mg/m2 twice daily on days 1–15 (28 doses) and B 15 mg/kg on day 1. Treatment was repeated every 21 days until progression. Eligibility criteria included HER2-negative MBC previously untreated for metastatic disease; ECOG performance status =1; no prior anti-angiogenic or oral fluoropyrimidine therapy. A sample size of 109 patients (including dropouts) was required to give 90% power to test an improvement from 4 months median PFS to 5.6 months with the two-sided test (a 5%) Results: At data cut-off, 103 patients had received study medication. Present results are based on 103 patients (ITT population), except tumor response which is based on 91 patients who had response evaluation. The average # of cycles received in first phase is 6.8. 84 pts.are alive at this time. 38.5% (35/91) pts. have had a response: complete response 5.5%; partial response 33.0%. Stable disease is 42.9% with 81.4% clinical benefit. Planned dose received is 77.7 % for C and 99.0 % for B. The majority of adverse events (AEs) were mild or moderate. The most common grade 3 AEs were hand-foot syndrome (13%) and pain (10%); grade 4 pulmonary embolism occurred in 2% in the first phase of the study. Conclusions: Updated results with longer follow-up including toxicity, TTP and PFS will be presented at the meeting. It appears that in first-line C+B is active for MBC and is well tolerated, with few grade 3/4 toxicities. [Table: see text]

Phase III Trial of Epirubicin Plus Paclitaxel Compared With Epirubicin Plus Cyclophosphamide As First-Line Chemotherapy for Metastatic Breast Cancer: United Kingdom National Cancer Research Institute Trial AB01

2005 ◽  
Vol 23 (33) ◽  
pp. 8322-8330 ◽  
Author(s):  
Ruth E. Langley ◽  
James Carmichael ◽  
Alison L. Jones ◽  
David A. Cameron ◽  
Wendi Qian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Survival Time ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
Line Chemotherapy

Purpose To compare the effectiveness and tolerability of epirubicin and paclitaxel (EP) with epirubicin and cyclophosphamide (EC) as first-line chemotherapy for metastatic breast cancer (MBC). Patients and Methods Patients previously untreated with chemotherapy (except for adjuvant therapy) were randomly assigned to receive either EP (epirubicin 75 mg/m2 and paclitaxel 200 mg/m2) or EC (epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for a maximum of six cycles. The primary outcome was progression-free survival; secondary outcome measures were overall survival, response rates, and toxicity. Results Between 1996 and 1999, 705 patients (353 EP patients and 352 EC patients) underwent random assignment. Patient characteristics were well matched between the two groups, and 71% of patients received six cycles of treatment. Objective response rates were 65% for the EP group and 55% for the EC group (P = .015). At the time of analysis, 641 patients (91%) had died. Median progression-free survival time was 7.0 months for the EP group and 7.1 months for the EC group (hazard ratio = 1.07; 95% CI, 0.92 to 1.24; P = .41), and median overall survival time was 13 months for the EP group and 14 months for the EC group (hazard ratio = 1.02; 95% CI, 0.87 to 1.19; P = .8). EP patients, compared with EC patients, had more grade 3 and 4 mucositis (6% v 2%, respectively; P = .0006) and grade 3 and 4 neurotoxicity (5% v 1%, respectively; P < .0001). Conclusion In terms of progression-free survival and overall survival, there was no evidence of a difference between EP and EC. The data demonstrate no additional advantage to using EP instead of EC as first-line chemotherapy for MBC in taxane-naïve patients.

Paclitaxel plus carboplatin versus paclitaxel plus epirubicin as first-line treatment for metastatic breast cancer: Efficacy and safety results of a randomized, phase III trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1087-1087
Author(s):  
Zhongsheng Tong ◽  
Shufen Li ◽  
Yehui Shi ◽  
Xu Wang ◽  
Chen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Significant Difference

1087 Background: Paclitaxel/carboplatin combinations are highly active in metastatic breast cancer (MBC). We conducted a randomized, phase III, non-inferiority trial comparing paclitaxel/carboplatin (TP) with paclitaxel/epirubicin (TE) as first-line therapy for MBC. Progression-free survival (PFS) was the primary efficacy endpoint. Secondary endpoints included response rate, overall survival, tolerability, and quality of life (QoL). Methods: From June 2009 to January 2015, 231 patients were randomly assigned, 115 of whom were randomized to TP and 116 to TE. Baseline characteristics were relatively well-balanced in the two treatments. Results: After a median follow-up of 29 months, no significant difference was observed between the two treatments in objective response rate (ORR) (38.3% vs. 39.7%, respectively). Both the progression-free survival (p=0.158) and overall survival (p=0.369) were very similar between the two treatments. Both regimens were well tolerated. The main toxicities were myelosuppression, gastrointestinal reactions, and alopecia. TP showed higher grades 3–4 alopecia and higher nausea (p<0.05). TE showed higher incidence of myelosuppression than TP (p<0.05) (Table). Those patients whose epirubicin cumulative dose was more than 1000 mg/m2 did not suffer worse cardiotoxicity. Conclusions: Our study suggests that TP arm is an effective therapeutic alternative for patients with MBC, especially in those previously exposed to epirubicin in the adjuvant setting. TP has some advantages, such as less cost and less side effects (myelosuppression and fatigue). Clinical trial information: NCT02207361. [Table: see text]

Safety and antitumor activity of 3-weekly anti-EpCAM antibody adecatumumab (MT201) in combination with docetaxel for patients with metastatic breast cancer: Results of a multicenter phase Ib trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1009-1009
Author(s):  
M. Sebastian ◽  
C. Hanusch ◽  
M. Schmidt ◽  
N. Marschner ◽  
D. Oruzio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Single Agent ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Epcam Expression ◽  
Secondary Objective ◽  
Grade 3

1009 Background: The fully human IgG1 antibody adecatumumab (MT201) binds to the epithelial cell adhesion molecule (EpCAM), which is expressed in over 90% of breast cancers and has been associated with poor prognosis. Data from a previous phase II study in metastatic breast cancer (MBC) indicated that single agent MT201 could prolong progression-free survival in a subset of patients with high EpCAM expression. This study tested safety and tolerability of MT201 treatment in combination with standard docetaxel. Methods: Relapsed or primary refractory, EpCAM-positive MBC patients were treated with docetaxel (100 mg/m2 q21d) in combination with MT201 (dose levels 180 mg/m2, and 550 mg/m2 q21d). A loading dose of 100 mg/m2 and 300 mg/m2, respectively, was administered on day 1 and 7. Patients were grouped into high- and low-level EpCAM expression. Primary objectives were safety and tolerability; anti-tumor activity according to RECIST was a secondary objective. Results: A total of 22 patients with a median of 3 prior chemotherapy lines were enrolled. Most frequent grade 3/4 adverse events (AE) in all patients were leucopenia (90%), neutropenia (77%), lymphopenia (68%), and diarrhea (23%). No evidence for aggravation of grade 3/4 toxicities typically associated with docetaxel was found. The dose level 550 mg/m2 q21d has been determined as MTD in combination with 100 mg/m2 q21d docetaxel. The overall response rate (CR/PR; RECIST) and clinical benefit rate (CR/PR and SD>24wks) in all evaluable patients was 24% and 41%, respectively. Patients with high EpCAM expression showed a response rate of 43%, whereas patients with low EpCAM expression had a response rate of 10%. Median time-to-progression (TTP) in all evaluable patients was 165 days. Conclusions: Combining MT201 with docetaxel for the treatment of MBC appears to be safe and feasible. The DLT of this combination were short and manageable episodes of grade 3 diarrhea. The response rate and TTP observed in this heavily pre-treated population is encouraging and warrant further development of MT201/chemotherapy combinations in patients with tumors of high EpCAM target level. [Table: see text]

Trastuzumab and Vinorelbine as First-Line Therapy for HER2-Overexpressing Metastatic Breast Cancer: Multicenter Phase II Trial With Clinical Outcomes, Analysis of Serum Tumor Markers as Predictive Factors, and Cardiac Surveillance Algorithm

2003 ◽  
Vol 21 (15) ◽  
pp. 2889-2895 ◽  
Author(s):  
Harold J. Burstein ◽  
Lyndsay N. Harris ◽  
P. Kelly Marcom ◽  
Rosemary Lambert-Falls ◽  
Kathleen Havlin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Ejection Fraction ◽  
Tumor Markers ◽  
Phase Ii ◽  
Response Rate ◽  
Metastatic Breast ◽  
First Line ◽  
Her2 Positive ◽  
Multicenter Phase

Purpose: Trastuzumab-based therapy improves survival for women with human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer. We conducted a multicenter phase II study to evaluate the efficacy and safety of trastuzumab combined with vinorelbine, and to assess cardiac surveillance algorithms and tumor markers as prognostic tools. Patients and Methods: Patients with HER2-positive (immunohistochemistry [IHC] 3+-positive or fluorescence in situ hybridization [FISH]-positive) metastatic breast cancer received first-line chemotherapy with trastuzumab and vinorelbine to determine response rate. Eligibility criteria were measurable disease and baseline ejection fraction ≥ 50%. Serial testing for HER2 extracellular domain (ECD) was performed. Results: Fifty-four women from 17 participating centers were entered onto the study. The overall response rate was 68% (95% confidence interval, 54% to 80%). Response rates were not affected by method of HER2 status determination (FISH v IHC) or by prior adjuvant chemotherapy. Median time to treatment failure was 5.6 months; 38% of patients were progression free after 1 year. Concurrent therapy was quite feasible with maintained dose-intensity. Patients received both chemotherapy and trastuzumab on 90% of scheduled treatment dates. Two patients experienced cardiotoxicity in excess of grade 1; one patient experienced symptomatic heart failure. A surveillance algorithm of screening left ventricular ejection fraction (LVEF) at 16 weeks successfully identified women at risk for experiencing cardiotoxicity. Other acute and chronic side effects were tolerable. Lack of decline in HER2 ECD during cycle 1 predicted tumor progression. Conclusion: Trastuzumab and vinorelbine constitute effective and well-tolerated first-line treatment for HER2-positive metastatic breast cancer. Patients with normal LVEF can be observed with surveillance of LVEF at 16 weeks to identify those at risk for cardiotoxicity.

Lapatinib with trastuzumab for heavily treated HER2-positive metastatic breast cancer (mBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11561-e11561
Author(s):  
Miguel J. Sotelo ◽  
Luis Manso ◽  
José Ángel Garcia Saenz ◽  
Eva M. Ciruelos ◽  
Fernando Moreno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Heavily Pretreated ◽  
Previously Treated ◽  
Grade 3

e11561 Background: Trastuzumab and lapatinib show complementary and non-cross resistant mechanisms of anti-HER2 action. Dual HER2 blockade has been preclinically and clinically assessed with encouraging results. Trastuzumab and lapatinib combination is effective in terms of survival in patients with heavily pretreated HER2-positive mBC. We aim to report our experience with lapatinib plus trastuzumab in this setting. Methods: Descriptive retrospective study of trastuzumab plus lapatinib activity in patients with HER2-overexpressing metastatic breast cancer treated in two institutions from 01/2007 to 12/2012. The objective of this analysis is to report the response rate (RR), progression-free survival (PFS) and toxicity. Results: 23 HER2-positive mBC patients previously treated with trastuzumab received trastuzumab plus lapatinib based therapy. 15 patients (65%) received 2 or more previous lines. 17 patients (74%) had visceral disease. Chemotherapy (CT) was added to the dual HER2 blockade treatment in 13 patients (56%) whereas hormonotherapy (HT) was added in 8 patients (35%) and 2 patients (9%) received lapatinib plus trastuzumab without any other agent. Chemotherapeutic drugs most used were: capecitabine (54%) and vinorelbine (15%). RR: partial response 22% (5/23), stable disease 39% (9/23). Median of follow-up was 11 months. PFS in the overall population was 4 months. PFS in patients with CT was 5 months, while PFS in patients with HT was only 2. PFS in hormone receptor positive and negative was 3 and 5 months respectively. The most common toxicities were: diarrhea (48%), anemia (39%), asthenia (39%) and hand-and-foot syndrome (17%). Grade ≥ 3 toxicity was diarrhea (26%) and hand-and-foot syndrome (9%). The incidence of cardiotoxicity was 9% (grade 2). Conclusions: These findings suggest that dual HER2 blockade in combination with CT is feasible and active in heavily pretreated HER2-positive mBC patients. However, further investigation is warranted to demonstrate superiority over sequential blockade with trastuzumab and lapatinib in this setting.

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