New Chemotherapy Agents Cut Advanced Breast Cancer Mortality in Half

IOANNINA, Greece, Dec. 9 (MedPage Today) -- Mortality in advanced breast cancer has decreased by as much as 50% with the use of newer combination chemotherapy regimens, results of a meta-analysis indicated.

The advent of anthracyclines led to a 22% reduction in mortality risk compared with older nonanthracycline drugs, John P. A. Ioannidis, M.D., of the University of Ioannina, and colleagues reported in the Dec. 17 issue of Journal of the National Cancer Institute.

The introduction of taxanes resulted in a 33% risk reduction compared with older single-agent therapy, and newer taxane-based combination regimens have reduced mortality by 51% as compared with single-agent regimens in use 35 years ago.

Clinicians also can offer patients a larger selection of chemotherapy regimens that have comparable efficacy.

"Stepwise improvements in efficacy of chemotherapy and targeted treatments cumulatively have achieved major improvements in the survival of patients with advanced breast cancer," the authors concluded. "Many options that can be used in first and subsequent lines of therapy have comparable efficacy profiles."

Although survival in advanced breast cancer has improved with the development of new chemotherapy regimens, the relative merits of many regimens have remained poorly defined, the authors noted.

Hundreds of clinical trials have compared regimens for advanced breast cancer, but each trial has evaluated only one or two treatment options. Because of that, "it is difficult to integrate information on the relative efficacy of all tested regimens."

In an effort to bring some clarity to the issue, Dr. Ioannidis and colleagues performed a systematic review and meta-analysis of studies involving chemotherapy and targeted treatment regimens for advanced breast cancer. Data were analyzed for individual trials, as well as for first- and second-line treatment.

The analysis involved survival data from 148 comparisons related to 122 clinical trials involving 26,031 patients and 22 different types of therapy.

All comparisons were against older, single-agent, nonanthracycline chemotherapy.

The authors found that anthracycline-based regimens reduced the mortality risk by 22% to 33% compared with older, nonanthracycline, single-drug regimens. Several newer regimens continued to build on the improvement achieved by anthracyclines. For example, single-drug taxane therapy was associated with a mortality hazard ratio of 0.67 (95% CI 0.55-0.81).

Anthracycline-taxane combinations reduced the mortality risk by 36% (HR 0.64, 95% CI 0.53-0.78), the authors continued.

Newer taxane-based combinations, such as those involving capecitabine (Xeloda) or gemcitabine (Gemzar), resulted in a mortality hazard ratio of 0.49 (95% CI 0.37-0.67), representing a 51% reduction in relative risk.

"Similar benefits were seen with several regimens including molecular targeted regimens," the authors said. "Most regimens had very similar efficacy profiles [<5% difference in HR] as first- and subsequent-line therapies."

Although useful from a historical perspective, the study has several limitations that detract from its generalizability, Martine J. Piccart-Gebhart, M.D., and Philippe L. Bedard, M.D., of Jules Bordet Institute in Brussels, Belgium, point out in an accompanying editorial.

Many of the studies included in the analysis involved too few patients to rule out heterogeneity and intertrial variability, they said. Moreover, the analysis is predicated on the assumption that trials with older agents that are no longer in widespread use are comparable to recent studies involving novel agents.

The authors also acknowledged that the effects of some regimens are "practically indistinguishable in magnitude," Drs. Piccart-Gebhart and Bedard continued.

"When several treatment options exist for the practicing clinician, an important goal of a mixed-treatment comparison is to provide a hierarchy of effect that can be used to guide treatment decisions," they added.

"Although this network meta-analysis is unlikely to alter routine clinical practice, it provides a solid evidence-based foundation to support the observation that the survival of women diagnosed with advanced breast cancer has improved because of more active systemic chemotherapy and targeted therapy," Drs. Piccart-Gebhart and Bedard concluded.

The authors and the editorialists reported no potential conflicts of interest.

Primary source: Journal of the National Cancer Institute Source reference: Ioannidis JPA et al. "Multiple-treatments meta-analysis of chemotherapy and targeted therapies in advanced breast cancer." J Natl Cancer Inst. 2008;100:1780-1791.Additional source: Journal of the National Cancer InstituteSource reference: Bedard PL, Piccart-Gebhart MJ. "Nonhormonal systemic therapy for advanced breast cancer: Do the math!" J Natl Cancer Inst. 2008;100:1745-1747.

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