Can Targeted Therapies and Chemotherapy Offer a Treatment Option in Triple-Negative Breast Cancers?

Targeted therapies used in conjunction with chemotherapy may offer benefits to patients with triple-negative breast cancer.

Targeted therapies combined with traditional chemotherapy led to higher progression-free survival rates in patients with triple-negative metastatic breast cancer, the results of a study suggest.

The study, published in the January 2014 edition of Core Evidence, found most targeted therapies increased patients’ progression-free survival rates when used in addition to their regular chemotherapy. The finding is particularly significant because patients with triple-negative cancers tend to have poor outcomes, and cannot be treated with endocrine or HER2-targeted therapies.

“The results of the metaanalysis showed that these patients might benefit from some of these new therapies: there were significant benefits in progression-free survival associated with bevacizumab, sorafenib, and iniparib, regardless of the line of treatment; however, cetuximab results are inconclusive so far,” the researchers wrote.

Despite the promising data on progression-free survival, researchers could not draw any conclusions about targeted therapies and chemotherapy and overall survival. The trials analyzed did not report overall survival rates consistently enough to draw concrete conclusions, they said.

Researchers analyzed results from 12 studies, which included a total of 2048 participants. Targeted therapies included bevacizumab, polyadenosine diphosphate-ribose polymerase (PARP) inhibition, sorafenib, cetuximab, and lapatinib.

An analysis of the bevacizumab studies showed better progression-free survival in patients treated with bevacizumab and chemotherapy than those who received only chemotherapy. One of the studies also showed a higher overall survival rate in participants receiving bevacizumab and chemotherapy; however, it was not deemed significant. Hematologic toxicities were similar between both treatment groups, and researchers noted proteinuria, hypertension, neuropathy, and bleeding events were reported more frequently in participants receiving chemotherapy and bevacizumab.

In studies comparing chemotherapy alone to chemotherapy and sorafenib, progression-free survival was also superior in participants receiving sorafenib and chemotherapy. Researchers found no difference in overall survival between the 2 groups. The proportions of hematologic toxicities were similar as well, although researchers noted more frequent hand or foot reactions and mucositis in participants receiving both therapies.

Cetuximab and chemotherapy elicited a better response rate than chemotherapy alone, and the study reporting progression-free survival found it was higher in participants receiving both therapies. Overall survival rate was similar between the treatment groups. Neutropenia and rash were seen more frequently in the cetuximab and chemotherapy group; however, other toxicities were reported at similar rates.

The single study evaluating lapatinib and chemotherapy found similar progression-free survival rates between the 2 groups.

A pooled analysis of the 2 studies evaluating chemotherapy with PARP inhibitors showed a higher response rate in participants receiving the combined treatment. The progression-free survival rate was higher in that group, as was the overall survival rate. Toxicities were similar between both groups.

The therapy combination requires further research, particularly in the area of overall survival rates.

“Despite these encouraging results, many unsolved questions remain regarding targeted therapies combined with chemotherapy in triple-negative breast cancer patients,” the researchers wrote. “There are still no answers for some important points: which is the most suitable chemotherapy scheme for the association, which are the best molecular-targeted therapies, how to determine the ideal treatment sequence, and the real impact of using targeted therapy combined with chemotherapy in overall survival.”