Role of Neoadjuvant Chemotherapy Evolving in TNBC

Melanie Majure, MD

The use of neoadjuvant chemotherapy to treat patients with triple-negative breast cancer (TNBC) is becoming more common and being explored in clinical trials, according to Melanie Majure, MD.

The role of neoadjuvant chemotherapy has evolved with a goal to achieve a pathologic complete response (pCR) to surgery, which has been associated with improved outcomes in clinical trials.

OncLive: Please provide an overview of your presentation on optimal chemotherapy use for patients with TNBC.

In an interview at the 2017 OncLive^® State of the Science Summit^TM on Breast Cancer, Majure, a clinical instructor, Department of Medicine, Division of Hematology/Oncology, the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, discussed the optimal role chemotherapy for patients with TNBC and the importance of achieving a pCR.Majure: I had the opportunity to speak about optimal chemotherapy regimens for TNBC. I focused my talk primarily on treatment in the early-stage setting, where I believe the data are most important. If you think about chemotherapy regimens in the metastatic setting, there has not been significant data to recommend 1 chemotherapy regimen over another.

I described what TNBC is and, in fact, it is not simply a tumor that does not have estrogen receptor, progesterone receptor, or HER2 overexpression. TNBC is a large group of disorders that do not have those biomarkers, but are distinct from one another. I mentioned the intrinsic subtypes that were demonstrated by Dr Brian D. Lehmann and others in 2011 and beyond. With those different intrinsic subtypes, we know that patients have a different prognosis as well as different responses to various therapies. It is important that we are aware of that, as we think about how to develop trials and look at response rates, particularly in the neoadjuvant setting for TNBC.

I spoke briefly about the adjuvant studies looking at the use of anthracyclines that were presented in the last few years. I discussed the ABC clinical trial that was presented at the 2016 ASCO Annual Meeting, the PlanB trial, and data from MINDACT that were presented at the 2017 ASCO Annual Meeting.

These studies are essentially asking the question of if we [can] avoid anthracyclines as an adjuvant therapy in patients who have higher risk HER2-negative breast cancer. The ABC trial demonstrated that in patients who have TNBC, particularly those patients with node-positive disease, that anthracyclines provided superior disease-free survival (DFS) over a standard 6 cycles of docetaxel/cyclophosphamide regimen.

However, the MINDACT trial and the PlanB study looked at similar populations comparing the use of docetaxel plus cyclophosphamide versus anthracycline and taxane regimens. Those studies demonstrated no difference in DFS or overall survival (OS). I began to ask the question of why those distinctions were seen in the results of those studies.

It was important to note that, in the ABC clinical trials, there was a higher percentage of TNBC than in the other 2 studies, where there were more node-positive patients. However, it is notable that molecular testing was used to investigate the randomized MINDACT study. More evaluation comparing those trials needs to happen, but it will take time. Most likely, the meta-analysis looking at these trials can help make the decision of whether we can get away without an anthracycline.

How has the role of chemotherapy evolved over the past few years?

I also discussed adding carboplatin in the neoadjuvant setting. There were 4 trials, the most important being CALGB 40603. That study essentially demonstrated improved rates of pCR with the addition of carboplatin, but had different results from other studies in terms of DFS. The phase II study was powered to demonstrate the impact on pCR, not on DFS.In the academic setting, we are not doing things differently. However, it is my impression that the use of neoadjuvant chemotherapy to treat TNBC is becoming more common. I see patients with metastatic recurrence who received surgery first and then go on to adjuvant chemotherapy, but we don’t know how those patients will do or what else to give them. It’s not so much a question of how the role of chemotherapy changes, but about the practice patterns of the rates of adjuvant treatment versus neoadjuvant use in TNBC.

In the last year, we have become more comfortable recommending patients to proceed with adjuvant capecitabine in the context of having residual disease after neoadjuvant chemotherapy. This is based off the CREATE-X trial, which has been published in the New England Journal of Medicine. This trial discusses significant additional benefits in both DFS and OS for patients with TNBC.