BCIRG 007: Randomized phase III trial of trastuzumab plus docetaxel with or without carboplatin first line in HER2 positive metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. LBA516-LBA516 ◽  
Author(s):  
J. F. Forbes ◽  
T. Pienkowski ◽  
V. Valero ◽  
W. Eiermann ◽  
G. Von Minckwitz ◽  
...  
Keyword(s):  
Metastatic Breast ◽  
Phase Iii ◽  
First Line ◽  
Her2 Positive ◽  
Phase Iii Trial ◽  
Efficacy Analysis ◽  
Significant Difference ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Taxane Chemotherapy

LBA516 Background: Based on preclinical synergism between docetaxel (T), carboplatin (C) and trastuzumab (H), BCIRG conducted a phase III trial for women with HER2+ MBC to evaluate efficacy and safety of H in combination with T or TC. Methods: 263 patients (pts) with HER2 FISH+ MBC were randomized to TH, (H with T 100 mg/m2) or TCH, (H with T 75 mg/m2 and C AUC=6). Chemo was given q3 wks for 8 cycles with wkly H at 2 mg/kg (loading dose of 4 mg/kg), followed by H q3 wks at 6 mg/kg until progression. Pts were stratified by centre and prior (neo) adjuvant taxane chemotherapy. Primary endpoint was TTP with 80% power (0.05 significance) to detect a 50% improvement in median TTP between the 2 arms. Secondary endpoints include overall survival, response rate, duration of response (DR), clinical benefit (CB) and safety. Results: 131 pts were treated in each arm. Pt characteristics were well balanced in both groups. Importantly, only 52% of pts received C at the protocol specified dose (RDI > 0.9). Efficacy analysis was conducted at 204 events. There was no significant difference between TH and TCH in median TTP (11.1 vs 10.4 mos, p = 0.57), ORR (73% in both arms), DR (10.7 vs 9.4 mos) and CB (67% in both arms). The most common gr 3/4 toxicities were: infection (44% vs 30%), neutropenic infection (22% vs 12%), thrombocytopenia (2% vs 15%), febrile neutropenia (12% vs 13%) asthenia (5% vs 12%), anemia (5% vs 11%), and diarrhea (2% vs 9%). Two pts died (1.5%) due to sepsis in TCH. Absolute LVEF decline > 15% were seen in 5.5% vs 6.7% of pts. One pt (0.8%) had a symptomatic CHF in TH arm Conclusions: The already effective TH regimen does not benefit from the addition of C, when the T dose in TH is 100 mg/m2 and 75 mg/m2 in TCH, in women with HER2+ MBC. No significant financial relationships to disclose.

BCIRG 007: First overall survival analysis of randomized phase III trial of trastuzumab plus docetaxel with or without carboplatin as first line therapy in HER2 amplified metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA1008-LBA1008 ◽  
Author(s):  
M. Pegram ◽  
J. Forbes ◽  
T. Pienkowski ◽  
V. Valero ◽  
W. Eiermann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Hematological Toxicity ◽  
Her2 Positive ◽  
Phase Iii Trial ◽  
Efficacy Analysis ◽  
First Line Therapy ◽  
Significant Difference

LBA1008 Background: Based on preclinical synergism between docetaxel (T), carboplatin (C) and trastuzumab (H), BCIRG conducted a phase III trial in HER2-positive MBC to evaluate efficacy and safety of H in combination with T or TC. Methods: 263 patients (pts) with HER2 FISH+ MBC were randomized to TH (H with T 100mg/m2) or TCH (H with T 75mg/m2 and C AUC=6). Chemotherapy was given every 3 weeks (q3w) for 8 cycles with weekly H at 2mg/kg (loading dose of 4 mg/kg) followed by H q3w at 6 mg/kg until progression. Pts were stratified by centre and prior (neo) adjuvant taxane chemotherapy. Primary endpoint was Time To disease Progression (TTP). Secondary endpoints include overall survival, response rate, duration of response (DR), clinical benefit (CB) and safety. Results: 131 pts were treated in each arm Pt characteristics were well balanced in both groups. A first efficacy analysis was conducted at 204 events. There was no significant difference between TH and TCH in median TTP (11.1 vs 10.4 mos, p=0.57), ORR (73% in both arms), DR (10.7 vs 9.4 mos) and CB (67% in both arms). At 39 months of median follow-up, median overall survival was 36.40 and 36.57 months in TH and TCH arms respectively. More patients on TCH received the max number of chemotherapy cycles, and numerically fewer patients on TCH discontinued treatment as a result of non hematological toxicity. The most common gr 3/4 toxicities were: Neutropenic infection that was 16.8% vs 9.2% respectively for TH and TCH, thrombocytopenia (2% vs 15%), asthenia (5% vs 12%), anemia (5% vs 11%), and diarrhea (2% vs 10%). Two pts died (1.5%) due to sepsis in TCH. Absolute LVEF decline > 15 % were seen in 5.5 % vs 6.7 % of pts. One pt (0.8%) had a symptomatic CHF in TH arm. Conclusion: Both TH (T 100) and TCH (T 75) were highly effective treatment regimens in women having HER2-positive MBC, demonstrating high response rates, median TTP > 10 months, and median overall survival > 36 months in both TH and TCH. Cardiac toxicity was no significant problem with either treatment. [Table: see text]

Phase II trial of vinorelbine (V) days 1+8 every 3 weeks and trastuzumab (T) weekly as first-line chemotherapy for HER2+ metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1091-1091
Author(s):  
M. Andersson ◽  
D. Nielsen ◽  
P. G. Sørensen ◽  
M. Ewertz
Keyword(s):  
Randomised Trial ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Phase Iii ◽  
Time To Progression ◽  
Phase Iii Trial ◽  
Highly Active ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Unacceptable Toxicity

1091 Background: Weekly V and T as 1. line therapy in patients (pts) with HER2+ MBC is highly effective with reported response rates (RR) from 61–86% and median time to progression (TTP) 8.5–16 months. This study examined V given twice every 3 weeks. Methods: Eligible pts had HER2+ (IHC 3+ or FISH) MBC with measurable disease by RECIST criteria, no prior chemotherapy or T for MBC, and LVEF > 50%. They received V 35 mg/m2 i.v. days 1+8 every 3 weeks (= 1 cycle) and T weekly (4 mg/kg loading dose, 2 mg/kg thereafter i.v.) until progression or unacceptable toxicity. Planned sample size was 50, but the study was replaced by a randomised trial at 46 pts, all of them eligible. Primary endpoint was RR, secondary endpoints included TTP, overall survival (OS) and toxicity. Results: From December 2001-July 2004 46 pts were recruited at 4 centers. They received 11 (1–54) cycles (median, range). V dose was reduced due to neutropenia in 7.5% of cycles and for other reasons in 14.5%. V treatment was delayed due to neutropenia in 7.8% of cycles and for other reasons in 4.7% of cycles. Median received V dose intensity was 0,78. Cardiotoxicity: asymptomatic reduction of LVEF > 20% or >10% to below 50%: 8 pts (3 to below 50%). Toxicity grade III-IV (pts): Neutropenia: 11. Infections: 5 (one septic death). Constipation 2. 43 pts have progressed and 32 have died. RR: CR: 9 (20%) PR: 13 (28%) SD 11 (24%) (SD> 6 months 9 (20%)) PD: 10 (22%) NE: 3 (7%). Median duration of response: 18.0 months. Median TTP: 11.0 months (95% confidence interval (95%CI) 7.6–14.4). Median OS: 25.4 months (95%CI 22.7–28.0). After progression 24 received docetaxel, 14 capecitabine, 6 epirubicine, and 11 endocrine therapy. Conclusions: V given twice every 3 weeks and T weekly is a highly active and well-tolerated 1. Line treatment for HER2+MBC. Recruitment into the trial was stopped at 46 pts in favor of a phase III-trial which is ongoing in the Nordic countries comparing V (days 1+8) + T with docetaxel+T every 3 weeks. No significant financial relationships to disclose.

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