For Residual TNBC Post-Chemo, Capecitabine Should Be Offered

Kathy D. Miller, MD


June 15, 2021

This transcript has been edited for clarity.

Hi. It's Dr Kathy Miller from Indiana University, with some more important news from the American Society of Clinical Oncology (ASCO) meeting for those of you who treat patients with breast cancer.

We worry about our patients who have triple-negative disease, especially those who have chemotherapy before surgery and still have residual disease. We know that this group has a very high risk for recurrence, and we've struggled with whether additional therapy would be helpful.

Many of us, myself included, were caught off guard several years ago when we saw the results of the CREATE-X trial. This well-done Japanese trial enrolled patients with ER-positive or triple-negative disease who received neoadjuvant therapy to capecitabine or not, and showed a significant reduction in distant recurrence, particularly in those patients with triple-negative disease.

We all sort of shook our heads and said, "Really? Capecitabine? Are you sure?"

There was not much uptake of that therapy. There was also a lot of skepticism about whether this was unique to Asian populations. Would this expand to a European genetic ethnic background population? Could we really do this?

We've seen two other studies since then, one most recently at ASCO, that say, "Yes, we can, and we really should because it helps our patients."

The first is a European-led trial that enrolled patients with high-risk, triple-negative, lymph node–positive disease who had completed adjuvant therapy. Patients were randomized to receive capecitabine for 1 year or not. These results also showed a significant reduction.

This year at ASCO, our colleague, Ingrid Mayer, reported the results of a trial led by ECOG-ACRIN that enrolled patients with triple-negative breast cancer who had residual disease following neoadjuvant therapy to either capecitabine or a platinum-based chemotherapy.

Ingrid's hypothesis was that, in the subset of patients with triple-negative disease who have basal subtype disease by gene profiling, platinum agents would be better. There is a wealth of preclinical data suggesting that might be the case.

The trial enrolled patients who had triple-negative disease with tumors. They did subtyping with the PAM50 test. They analyzed the results overall, and then also separately in the basal subtype — about 70% of the population — and the nonbasal subtype.

For the entire population, there really was no suggestion that platinum agents were better. There was no suggestion that they were better or even that they were not inferior in the basal subtype. In the nonbasal subtype, they looked worse. Capecitabine really was superior therapy, and platinum agents had more toxicity.

Great science, put to the test in the clinic, didn't work. Our hypothesis was wrong. Perhaps the most important lesson from this trial is that the authors of CREATE-X were right.

Now, Ingrid's trial cannot tell us the magnitude of the benefit of capecitabine. But unless you think platinum agents are overtly harmful — not only that they're toxic but also that they're harmful in that they increase the risk for recurrence — there was no way around the fact that we simply have to conclude that capecitabine is helpful. We need to accept this as the standard of care. It ought to be offered to all high-risk patients with triple-negative disease who have residual disease after neoadjuvant therapy.

It also tells us that this is a really high-risk group. There is much more work to do and more room for improvement. We will continue to look at other clinical trials of novel approaches in this group.

I hope you all had a good weekend at ASCO. I am so looking forward to seeing everybody in person next year.

This is Dr Kathy Miller from Indiana University.

Kathy D. Miller, MD, is associate director of clinical research and co-director of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University. Her career has combined both laboratory and clinical research in breast cancer.

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