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Here's a start. If I can post the entire article, I’ll finish up in a second post.
Results of Second Planned Interim Analysis of Phase III Study: BCIRG 006
SAN ANTONIO, Dec. 14 /PRNewswire-FirstCall/ -- The Cancer International Research Group (CIRG) and sanofi-aventis today announced the results from the second interim efficacy and safety analysis from the BCIRG 006 Phase III breast cancer study, which confirms, at a 3-year median follow-up, that Herceptin(R) combined with Taxotere(R)-based regimens significantly improved disease-free survival for women with early HER2-positive breast cancer.<o></o>
The BCIRG 006 study randomized patients to receive the control arm AC-T [4 cycles of doxorubicin (A) and cyclophosphamide (C) followed by 4 cycles of Taxotere(R) (T)], or either of two experimental Herceptin(R)-(H) an<o></o>>
Taxotere(R)- based therapies: AC-TH (adds 1 year of Herceptin(R) treatment to the AC-T regimen with Herceptin(R) starting concurrently with Taxotere(R)), or TCH (6 cycles of Taxotere(R) and carboplatin (C) with 1 year of Herceptin(R) starting at the first cycle). Patients were
prospectively stratified according to their nodal status and hormone <o></o>receptor status.<o></o>
The primary endpoint was disease-free survival (DFS). Secondary<o> </o>endpoints included overall survival (OS), safety, including cardiotoxicity, and pathologic and molecular markers. The safety analysis was performed by an Independent Data Monitoring Committee.<o></o>
In terms of a reduction in the risk of death, 41% (p < 0.0041) and 34% (p < 0.017) of patients in the AC-TH and TCH arms, respectively when compared with the non-Herceptin-containing control arm. The relative
reduction in the risk of relapse was 39% (p < 0.001) and 33% (p = 0.0003) for AC-TH and TCH respectively vs. control. This interim analysis showed that 92% and 91% of patients were alive at 4 years in the herceptin/Taxotere-containing arms (AC- TH and TCH) respectively compared to 86% in the AC-T arm. Of note, TCH (combination of Taxotere(R)/carboplatin/Herceptin(R)), the regimen without anthracycline, demonstrated similarly significant improvement in disease free and overall survival as the AC-TH arm. However, the TCH arm yielded a five- fold decrease in significant cardiotoxicity when compared to the
anthracycline/Herceptin(R)-containing arm.<o></o>
These data were presented at the 29th annual San Antonio Breast Cancer Symposium (SABCS) in San Antonio, TX - USA.<o></o>
"This trial demonstrates an optimal therapeutic index for these patients with the use of TCH (which did not include doxorubicin), thus avoiding the significant cardiac damage related to the sequential use of
anthracyclines and Herceptin(R)," said Dennis Slamon, PhD, MD, Co-Chair of the BCIRG 006 study and Director of Clinical and Translational Research at UCLA's Jonsson Comprehensive Cancer Center. "In this interim analysis, 6 cycles of chemotherapy in the TCH regimen provided similar benefit as AC-TH (8 cycles of chemotherapy in total) without increasing cardiotoxicity. In addition, no secondary leukemias have been observed so far in the TCH arm compared to four leukemia events in the anthracycline-containing arms, although further long term hematologic adverse event follow up will continue. These data should help influence daily practice with TCH being considered an option for women with early stage HER2 positive breast cancer, irrespective of nodal status."<o></o>
The cardiac toxicity of the 2 experimental arms significantly favored the TCH regimen. No cardiac deaths were observed in either arm. There were 20 congestive heart failure events in AC-TH versus four in the TCH arm. Moreover, there were 50% fewer asymptomatic declines in cardiac function in the TCH arm as compared to AC-TH. Also, in terms of other toxicities, the TCH arm appeared to be superior to AC-TH with regards to the main toxicities in particular sensory neuropathy (36.1% vs 49.7%), nail changes (28.7% vs 43.6%), and myalgia (38.6% vs 55.5%). However, more grade 3 and 4 thrombocytopenia (5.4% vs 1.2%) and anemia (5.8% vs 3.1%), were observed in the TCH arm compared to the AC-TH arm.<o></o>
About the BCIRG 006 Study The BCIRG 006 study was designed to maximize efficacy while minimizing toxicity in adjuvant Herceptin(R)-based therapies. Between April 2001 and March 2004, the study enrolled 3, 222 women with early stage HER2-positive breast cancer, with positive axillary lymph nodes (LN) as well as those without LN involvement.<o></o>
In this second interim analysis, at a 3-year median follow-up, AC-TH and TCH significantly improved DFS and OS as compared to the control arm. The relative reduction in the risk of relapse was 39% (p < 0.001) and 33% (p = 0.0003) respectively, for AC-TH and TCH vs control. The relative reduction in the risk of death was 41% (p < 0.0041) and 34% (p < 0.017)respectively, for AC-TH and TCH vs control.<o></o>
In addition, the absolute DFS benefit at 4 years is similar for the two Herceptin(R)-containing arms (6% and 5% for AC-TH and TCH, respectively). Notably, the same level of DFS and OS benefit was also obtained for the 29% of node negative patients enrolled in the study.<o></o>
In terms of safety, there was a significant difference in the major toxicity that has been consistently seen with Herceptin(R)-based therapies i.e. cardiac toxicity. Common to all of the Herceptin(R) adjuvant trials was the evaluation of congestive heart failure and cardiac-related deaths. As mentioned above, the cardiac toxicity of the 2 experimental arms significantly favored the TCH regimen. Further, in terms of other toxicities, the TCH regimen appeared to also be superior to the AC-TH arm.<o></o>
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