A study presented by Dr. Andrew Tutt at the 2014 San Antonio Breast Cancer Symposium conference is interesting because it is the first to compare platinum-based chemotherapy with taxanes in women with metastatic breast cancer. As both of these drug classes are toxic, a study like this could be very helpful if the results could help direct therapy to reduce or minimize toxicity while still treating triple negative breast cancer (TNBC) effectively (in other words, could women take the less toxic of the two treatments and still get the same results?) Also included in the study was a subset of women who were known to be BRCA 1 or 2 mutation carriers — yielding some findings that suggest a potential new standard if treatment for these patients. These results could provide valuable information for a woman and her clinician to use when making decisions about which chemotherapy drug to choose.
The study randomized 376 patients from 74 centers across the United Kingdom – of which 29 were known to carry BRCA 1 or 2 mutations. The average age of women in the study was 55, median follow-up was 11 months, and women were excluded if they had received taxen-based therapies in the past 12 months.
For the non-BRCA mutation carriers, the researchers used objective response (ORR) as an endpoint; for the BRCA carriers they measured disease free survival (DFS). ORR is the proportion of patients who show either complete response (CR) or partial response (PR). DFS measures the length of time a patient goes without showing any progression of her disease.
The study results showed a number of things. One was that in terms of toxicity and side-effects, women tolerated carboplatin better than docetaxel. This was not a surprise, as the differences in the toxicities of these two drugs are well known. Additionally the study found that on average there is no significant ORR difference between the two treatment groups (32% for carbo and 36% for docetaxel). The median survival was 12 months in both groups.
While the subset of BRCA carriers also showed no difference in DFS (4.8 months for carboplatin and 5.2 months for docetaxel respectively) this group did show a difference in ORR (68% for carboplatin vs. 33% in docetaxel group). This underscores findings from previous studies indicating that BRCA-mutation associated breast cancers are particularly responsive to platinum-based chemotherapies.
There are some important learnings from this study which can be used when guiding therapy for women with metastatic or recurrent locally advanced TNBC. First, there is no evidence of superior OS or DFS response to carboplatin vs docetaxel in unselected TNBC — therefore the therapy can be selected based on the least toxic treatment. However patients with BRCA 1 or 2 mutations being treated for metastatic or recurrent locally advanced TNBC may get better results
S3-01. The TNT trial: A randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer (CRUK/07/012)