HER2 Support Group Forums - View Single Post - Dr. Slamon's 10-6-11 NEJM review on Herceptin

Hopeful · 10-06-2011, 07:41 AM

http://www.nejm.org/doi/full/10.1056...TOC#t=abstract

From the full article:

"The emerging further understanding of longterm and life-altering toxic effects associated with adjuvant anthracyclines may provide the most compelling support for nonanthracycline regimens. The well-known, long-term side effects of anthracyclines include significantly increased risks of congestive heart failure, myelodysplasia, and acute leukemia. However, recent analyses
of the National Cancer Institute Surveillance, Epidemiology,and End Results (SEER) database indicate that we may be underestimating the full effect of anthracycline use on long-term cardiac and hematologic health in patients treated for breast cancer with these agents, possibly because the majority of adjuvant studies have been designed primarily to evaluate differences in efficacy and have used follow-up periods of 7 to 10 years for both efficacy and safety analyses. Attempts to obtain longer-term safety data, including cardiac outcomes, are systematically biased by loss of later follow-up.

In addition, the SEER database is derived from information on women 65 years of age or older. The mean age of women in the HER2-positive adjuvant studies was 51 to 52 years, whereas the
mean age of the overall breast-cancer population is approximately 62 years. Given that data from our study and other trials show that trastuzumab augments the incidence of anthracycline-associated congestive heart failure and subclinical loss of LVEF, the full effect of any nonsymptomatic damage induced by the combination of trastuzumab with anthracycline-based regimens may not be apparent until much later as these younger women have additional, age-related cardiac insults. Our findings on long-term, subclinical LVEF losses, as well as the published results from the SEER database analyses, involving some 42,000 women, support this concern.

Furthermore, although myeloid growth factors permit delivery of full-dose, accelerated- schedule adjuvant anthracycline cyclophosphamide treatments, registry data suggest a doubling of the incidences of acute leukemia and myelodysplasia associated with these regimens, though the absolute risk remains low. Of note, all cases of acute leukemia in our study occurred in patients who had previously been exposed to an anthracycline. Some observers have argued that these major toxic effects are rare and are offset by significant efficacy gains obtained with anthracyclines. However, our data do not fully support this argument. We did not find any significant incremental therapeutic benefits of combined trastuzumab–anthracycline treatment as compared with TCH, yet we did see significant increases in both acute and chronic toxic effects with the trastuzumab–anthracycline regimen. Consequently, we believe that TCH offers an effective alternative to the anthracycline-based regimens and their associated risks."

Hopeful

10-06-2011, 07:41 AM	#1
Hopeful Senior Member Join Date: Aug 2006 Posts: 3,380	Dr. Slamon's 10-6-11 NEJM review on Herceptin http://www.nejm.org/doi/full/10.1056...TOC#t=abstract From the full article: "The emerging further understanding of longterm and life-altering toxic effects associated with adjuvant anthracyclines may provide the most compelling support for nonanthracycline regimens. The well-known, long-term side effects of anthracyclines include significantly increased risks of congestive heart failure, myelodysplasia, and acute leukemia. However, recent analyses of the National Cancer Institute Surveillance, Epidemiology,and End Results (SEER) database indicate that we may be underestimating the full effect of anthracycline use on long-term cardiac and hematologic health in patients treated for breast cancer with these agents, possibly because the majority of adjuvant studies have been designed primarily to evaluate differences in efficacy and have used follow-up periods of 7 to 10 years for both efficacy and safety analyses. Attempts to obtain longer-term safety data, including cardiac outcomes, are systematically biased by loss of later follow-up. In addition, the SEER database is derived from information on women 65 years of age or older. The mean age of women in the HER2-positive adjuvant studies was 51 to 52 years, whereas the mean age of the overall breast-cancer population is approximately 62 years. Given that data from our study and other trials show that trastuzumab augments the incidence of anthracycline-associated congestive heart failure and subclinical loss of LVEF, the full effect of any nonsymptomatic damage induced by the combination of trastuzumab with anthracycline-based regimens may not be apparent until much later as these younger women have additional, age-related cardiac insults. Our findings on long-term, subclinical LVEF losses, as well as the published results from the SEER database analyses, involving some 42,000 women, support this concern. Furthermore, although myeloid growth factors permit delivery of full-dose, accelerated- schedule adjuvant anthracycline cyclophosphamide treatments, registry data suggest a doubling of the incidences of acute leukemia and myelodysplasia associated with these regimens, though the absolute risk remains low. Of note, all cases of acute leukemia in our study occurred in patients who had previously been exposed to an anthracycline. Some observers have argued that these major toxic effects are rare and are offset by significant efficacy gains obtained with anthracyclines. However, our data do not fully support this argument. We did not find any significant incremental therapeutic benefits of combined trastuzumab–anthracycline treatment as compared with TCH, yet we did see significant increases in both acute and chronic toxic effects with the trastuzumab–anthracycline regimen. Consequently, we believe that TCH offers an effective alternative to the anthracycline-based regimens and their associated risks." Hopeful Last edited by Hopeful; 10-06-2011 at 07:46 AM..