Some postings by Musa Mayer, Author, Advocate You may recall that at last year's San Antonio meeting, we heard the provocative findings of the FinHER study, a trial from Finland that looked at 9 weeks of adjuvant Herceptin in combination with docetaxel or vinorelbine following CEF in a subset of HER2+ high-risk primary breast cancer patients. Though the numbers randomized were small (232), the improvement in outcome of the patients randomized to the 9 weeks of Herceptin appeared similar to that in the large adjuvant Herceptin trials, raising the question of whether 9 weeks of Herceptin might not be enough. This year, there was another important but not definitive finding for short duration Herceptin, this time from George Sledge, who presented a poster of E2198 (abstract below), an adjuvant Herceptin safety study looking at cardiotoxicity of prior administration of Herceptin and Taxol, before Adriamycin and Cytoxan. While the two arms of this 234 woman study differed in the duration of Herceptin--9 weeks vs. 1 year--overall survival at 5 years was the same. He concludes: "Although not designed or powered to test the question of trastuzumab duration, E2198 does not show a significant advantage for prolonged trastuzumab administration." Obviously, further research on Herceptin duration is needed, as both cost and cardiotoxicity are at stake, and there are many countries that simply can't afford to offer women with HER2+ breast cancer adjuvant Herceptin of a year's duration. There was talk in San Antonio of a German study to answer the question, and we know that France is currently enrolling a multicenter 7,000 woman trial entitled "Trastuzumab for 6 Months or 1 Year in Treating Women With Nonmetastatic Breast Cancer That Can Be Removed By Surgery." This trial randomizes women with HER2+ breast cancer who have been treated with 4 cycles of unspecified chemo and begun their year of Herceptin, and randomizes them to continue only to 6 months vs. completing the full year of Herceptin. Talk by Dennis Slamon, UCLA/Revlon Ctr. Because there were some striking new findings here, I thought I'd summarize Dennis Slamon's excellent presentation of the update of the BCIRG 006 study, one of the four large adjuvant trials that looking at various ways of incorporating adjuvant Herceptin. It's worth noting that NBCC partnered with BCIRG on this randomized controlled trial as part of their clinical trials initiative, and that breast cancer advocates were involved at every stage of this trial. BCIRG 006 tested adjuvant Herceptin as adjuvant treatment in over three thousand node positive or high risk node-negative HER2+ primary breast cancer patients, enrolled from 2001-2004. Here are the three arms of the study, which was stratified by nodes and hormonal receptor status: ** AC-T (4 x AC followed by 4 x Taxotere) ** AC-TH (same as above followed by one year Herceptin given weekly) **TCH (6 x Taxotere and Carboplatin, followed by one year Herceptin) The primary endpoint was disease-free survival (DFS), plus secondary endpoints: overall survival (OS), toxicity and pathologic and molecular markers. 29% of patients were high-risk node negative. Because the trial was NOT stopped early, only 17 patients, or1.6% of 1,073 randomized to the control arm, crossed over to receive Herceptin, leaving 98.4% of the intention to treat group intact. This offers a much clearer picture of efficacy. At the first interim analysis after 23 months, presented at last year's SABCS, there had been 322 DFS events and 84 deaths. At the second interim analysis last month, after 36 months, there have been 462 DFS events and 185 deaths. While not statistically significant, it looked as if the AC-TH arm might surpass both the TCH arm and the AC-T arm. The second interim analysis told another story, however. Now both of the taxane-containing arms with Herceptin are showing marked improvement in DFS (AC-TH 83% and TCH 82%) over the non-Herceptin arm (AC-T 77%) . Overall survival takes into account other causes of death, and can capture serious toxicities of treatment. Again, the AC-T arm is inferior to both Herceptin-containing arms, with AC-TH at 92% and TCH at 91% (a non-significant difference), while AC-T is only at 86%. These findings were pretty much true for all subpopulations: of node+ and node- as well as HR+ and HR-, and regardless of tumor size. Overall the TCH was the least toxic of the regimens across almost all areas, including leukemia, where there were four cases in the two anthracycline-containing arms. Not surprisingly, there was significantly less cardiotoxicity in the TCH arm, even less than the AC-T arm. Left ventricular ejection fraction was higher in the TCH arm, even two years later. Though still small in numbers (20 patients) grade 3-4 congestive heart failure was four times higher in the AC-TH arm than in the other arms. I'll close by citing Dennis Slamon's own words: "In addition, 23 patients with bona fide HER2 amplification who were randomized to the AC-TH arm never got trastuzumab due to unacceptable declines in LVEF before receiving the antibody. "Considering the recently published data from US Oncology showing a highly statistically significant superiority of docetaxel-cyclophosphamide (TC) over adriamycin-cyclosphosphamide (AC) in terms of breast cancer efficacy (Jones, S. JCO 24:5381,2006), the BCIRG 006 update for HER2 positive malignancies shows the difference in number of DFS events and breast cancer deaths in favor of AC-TH, neither of which are statistically significant, is now exceeded by the number of critical adverse events. These include grade III/IV CHF and AC-related leukemia as well as a small and sustained loss of LVEF for 18% (189 patients) both of which are highly statistically significant.... "What is the role of anthracyclines in the adjuvant treatment of breast cancer?" These slides can be seen at http://tinyurl.com/tboaq See more on Herceptin, HER2, etc. in articles below. Pooled Analysis on Interaction HER-2 Expression & Adjv Chemo Abstract #41 Breast cancer in Pacific Island women Abstract #6062 SABCS 12/06 ER receptors, HER2 Status & Bodyweight Abstract #6064 SABCS 12/06 HER2/neu (E75) vaccine for prevention of recurrence Abstract #4 SABCS 12/06 Remember we are NOT Doctors and have NO medical training. 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