Impact of non-hormonal therapies on survival in advanced breast cancer

A systematic review and network meta-analysis has attempted to quantify the relative merits of systemic non-hormonal therapies in prolonging survival in advanced breast cancer.

Researchers searched for studies of different regimens involving chemotherapy and/or targeted therapy in advanced breast cancer published between 1973 and 2007. They identified 370 eligible randomised trials (54,189 patients), of which 172 (31,552 patients) compared different types of treatment. Survival data from 148 comparisons pertaining to 128 of the 172 trials (26,031 patients, 22 different types of treatment) were available for inclusion in the multiple-treatments (network) meta-analysis.

In contrast to a traditional meta-analysis that directly compares two interventions by pooling data only from trials asking a similar question, a network meta-analysis also incorporates indirect comparisons of multiple interventions from trials that differ widely in design using a statistical methodology that respects random assignment.

Hazard ratios (HR) were calculated for each treatment category relative to monotherapy with old agents (i.e. regimens not including anthracyclines, anthracenediones, vinorelbine, gemcitabine, capecitabine, taxanes, marimastat, thalidomide, trastuzumab, lapatinib, or bevacizumab).

Compared with single-agent chemotherapy with old non-anthracycline drugs, anthracycline regimens achieved 22% to 33% relative risk reductions in mortality (HR for standard-dose anthracycline-based combination = 0.67, 95% credibility interval [CrI] 0.57 to 0.78). Several newer regimens achieved further benefits:

• Single-drug taxane, 0.67; 0.55 to 0.81
• Combination of anthracyclines with taxane, 0.64; 0.53 to 0.78
• Taxane-based combination with capecitabine or gemcitabine, 0.49; 0.37 to 0.67

Similar benefits were seen with several regimens including molecular targeted treatments and most regimens had similar efficacy profiles (< 5% difference in HR) as first- and subsequent-line therapies.

The researchers conclude from these findings that “stepwise improvements in efficacy of chemotherapy and targeted treatments cumulatively have achieved major improvements in the survival of patients with advanced breast cancer. Many options that can be used in first and subsequent lines of therapy have comparable efficacy profiles.”

An accompanying editorial notes that the main finding of this labour-intensive piece of work is that “many classes of modern breast cancer therapy, including anthracyclines, taxanes, novel nontaxanes, and trastuzumab, either as monotherapy or as combination therapy would produce tangible gains in absolute survival over older single agents, ranging from 4.2 to 12.5 months for a patient with an anticipated survival of 1 year treated with the reference standard alone.” The authors add that though this study provides an important historical perspective and a framework for interpreting future advances in breast cancer therapy, it has a number of limitations that should be acknowledged. Furthermore, the findings are unlikely to alter routine clinical practice, but do provide 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.