Rutgers Cancer Institute of New Jersey (NJ, USA) investigators recently presented data from a Phase II clinical trial demonstrating that a combination of doxil, carboplatin and bevacizumab is a well-tolerated treatment regimen for metastatic triple-negative breast cancer.
The platinum-based regimen was trialled in patients who had not received prior treatment for their metastatic disease and genomic profiling was included in order to identify potential markers of response. The results were presented at the 2014 San Antonio Breast Cancer Symposium (9–13 December, TX, USA).
“With up to 20% of breast cancer cases diagnosed as triple negative, additional treatment options are needed for this population,” noted lead author and co-investigator Kim M Hirshfield (Rutgers Cancer Institute of New Jersey). “By exploring nontraditional agents and integrating genomic analysis, we have an opportunity to expand our arsenal of therapies against this disease.”
Owing to the fact that triple-negative breast cancers are often deficient in DNA repair, there is mounting evidence suggesting that DNA- damaging platinum agents may offer improved outcomes in treating this subset of the disease.
The Rutgers team examined this theory further in this trial, recruiting 31 patients with untreated metastatic triple-negative breast cancer between 2008 and 2012. These participating patients received a combination of doxil, bevacizumab and carboplatin once every 4 weeks for a median of 5.6 treatment cycles.
Approximately 39% of participants experienced a clinical response that lasted at least 6 months. Taxane therapy was included as part of the treatment of primary disease in 41.9% of the individuals. Approximately 31% of participants who received prior taxane therapy experienced a clinical benefit of greater than 6 months.
Median progression-free survival was 5.6 months, while the percentage of patients who had not progressed at 6 months was 41.9%. Median overall survival was 11.9 months and the 1-year survival rate was 47.3% with 13 patients alive at 10 months or longer. Bevacizumab was discontinued from the regimen as two patients experienced severe hypertension and one patient experienced a symptomatic blood clot.
“While the regimen demonstrated a clinical benefit, it was also well tolerated, as women experienced minimal nausea and did not experience hair loss. That speaks to an improved quality of life,” commented the study’s principal investigator Deborah Toppmeyer (Rutgers Cancer Institute of New Jersey).
Analysis of the tumors by next-generation sequencing highlighted p53 alterations to be the most common genetic abnormality present. In three individuals, there was an increase in the number of genomic alterations noted at the time of disease progression.
“By uncovering specific genomic abnormalities, we can identify molecularly targeted cancer treatments. In this particular case, our data may provide a better understanding about p53 biomarkers in terms of their sensitivity to platinum-based agents and how we can use that information to tailor therapy regimens for triple-negative breast cancer patients,” concluded Hirshfield.