Skip to main content
Premium Trial:

Request an Annual Quote

This Week in NEJM: Jan 26, 2012


In NEJM this week, a team of German researchers report a study of neoadjuvant chemotherapy combined with bevacizumab for the treatment of HER2-negative breast cancer. The team randomly assigned 1,948 patients to receive neoadjuvant epirubicin and cyclophosphamide followed by docetaxel, either with or without concomitant bevacizumab. Overall, the patients in the control group had a pathological complete response rate of 14.9 percent, compared to 18.4 percent in the bevacizumab group. Among the subgroup of 663 patients with triple-negative tumors, the pathological complete response rate was 27.9 percent in the control group and 39.3 percent in the bevacizumab group. "The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer," the authors write. "Efficacy was restricted primarily to patients with triple-negative tumors, in whom the pathological complete response is considered to be a reliable predictor of long-term outcome."

Also in NEJM this week, a group of American and Canadian researchers report a study of bevacizumab in combination with several chemotherapy regimens for the treatment of HER2-negative breast cancer. The team randomly assigned 1,206 patients to receive neoadjuvant chemotherapy consisting of docetaxel alone, docetaxel plus capecitabine, or docetaxel plus gemcitabine, with all regimens to be followed by doxorubicin-cyclophosphamide treatment, and either with or without the addition of bevacizumab. The team found that the addition of capecitabine or gemcitabine to docetaxel therapy did not significantly increase the rate of pathological complete response, as compared to docetaxel alone. However, the team also found that the addition of bevacizumab significantly increased the rate of pathological complete response.

In a related editorial in NEJM this week, the University of Miami Sylvester Comprehensive Cancer Center's Alberto Montero and Charles Vogel say the ongoing controversy over whether bevacizumab effectively treats metastatic breast cancer "goes beyond the science of tumor angiogenesis and involves broader questions about the use of surrogate end points in clinical trials, as well as economic arguments over the ever-increasing cost of new medicines for the treatment of cancer." Although both new studies into bevacizumab's efficacy use the endpoint of pathological complete response, the two teams used different definitions of the term, with the first team defining it as an absence of residual tumor in the breast and nodes and the second team defining it as absence of residual tumor in the breast only. In addition, Montero and Vogel say, these two trials used docetaxel-based chemotherapy regimens rather than paclitaxel regimens that bevacizumab was originally tested with. "These two well-performed trials do not resolve existing controversies surrounding bevacizumab therapy," the authors add. "If surrogate end points like progression-free survival in patients with metastatic breast cancer and pathological complete response in the neoadjuvant setting are ultimately predictive of survival benefits in earlier-stage disease, then the use of these surrogates in clinical research will be vindicated. ... However, in the context of unsustainable expenditures for cancer care in the United States, any survival benefit of bevacizumab, or other molecularly targeted drugs, will be balanced against the considerable development costs of modern molecularly targeted oncology drugs."

The Scan

Myotonic Dystrophy Repeat Detected in Family Genome Sequencing Analysis

While sequencing individuals from a multi-generation family, researchers identified a myotonic dystrophy type 2-related short tandem repeat in the European Journal of Human Genetics.

TB Resistance Insights Gleaned From Genome Sequence, Antimicrobial Response Assays

Researchers in PLOS Biology explore M. tuberculosis resistance with a combination of sequencing and assays looking at the minimum inhibitory concentrations of 13 drugs.

Mendelian Disease Genes Prioritized Using Tissue-Specific Expression Clues

Mendelian gene candidates could be flagged for further functional analyses based on tissue-specific transcriptome and proteome profiles, a new Journal of Human Genetics paper says.

Single-Cell Sequencing Points to Embryo Mosaicism

Mosaicism may affect preimplantation genetic tests for aneuploidy, a single-cell sequencing-based analysis of almost three dozen embryos in PLOS Genetics finds.