A new study has reported that non-anthracycline chemotherapy plus one year of Herceptin (trastuzumab) after breast cancer surgery significantly improves breast cancer-free and overall survival among women with HER2 overexpressing (HER2+) breast cancer. The study was designed to investigate the efficacy and safety of a new non-anthracycline regimen including Herceptin in treating HER2+ breast cancer. Herceptin improves survival in the adjuvant treatment of HER2+ breast cancer. However, Herceptin combined with anthracyclines has been associated with heart damage.
The study included 3,222 women with early-stage HER2+ breast cancer. Participants were randomly assigned to receive either (1) doxorubicin (Adriamycin, an anthracycline) and cyclophosphamide followed by docetaxel (Taxotere, a taxane) every three weeks (AC-T chemotherapy); (2) the same regimen plus 52 weeks of Herceptin (AC-T plus Herceptin); or (3) docetaxel and carboplatin (Paraplatin, a platinum salt) plus 52 weeks of Herceptin (TCH). Breast cancer-free survival was the primary study end point. Secondary end points were safety and overall survival.
The estimated five-year disease-free survival rate was 75% among those receiving AC-T, 84% among participants receiving AC-T plus Herceptin, and 81% among those receiving TCH. The corresponding estimated rates of overall survival were 87%, 92%, and 91%, respectively. There were no significant differences in cancer-free or overall survival between the two Herceptin regimens, while both were superior to AC-T. In addition, the safety of AC-T was lower. The rates of congestive heart failure and cardiac dysfunction were found to be significantly higher in the AC-T plus Herceptin group than in the TCH group. Eight cases of acute leukemia were reported among women exposed to an anthracycline. The authors conclude that the addition of one year of adjuvant Herceptin significantly improved disease-free and overall survival among women with HER2 positive breast cancer. The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus Herceptin, given its similar effectiveness, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia.
In a separate interview, study lead author Dr. Dennis Slamon said, “Given the data in this study, it makes one really question what role Adriamycin should play in the treatment of HER-2 positive early breast cancer, or in the treatment of early breast cancer at all . . . This trial should impact the way these breast cancers are treated, with a non-anthracycline regimen being our preferred option. I think this is a change that is going to be slow in coming, unfortunately, as many of our adjuvant treatments for breast cancer are built on the backbone of anthracyclines. While they’re effective, whatever gain patients may receive is more than made up for in the serious and chronic long-term side effects.” However, not all observors agree with this conclusion and the study results appear to be partially contradicted by another recent study (see the second study below).