Adjuvant IO Fails in BRCA+ Breast Cancer Patient; Now What?

Kathy D. Miller, MD


October 01, 2021

This transcript has been edited for clarity.

Hi. It's Dr Kathy Miller, and I am thinking about a patient scenario that you're going to encounter in your practice before too long. Imagine a patient with triple-negative breast cancer coming in with stage II disease, maybe a palpable or a biopsy-proven lymph node. Based on the KEYNOTE-522 data, I think you're going to recommend neoadjuvant chemotherapy with a checkpoint inhibitor.

Imagine if this patient does not achieve a pathologic complete response. The KEYNOTE-522 trial gave the immune checkpoint inhibitor for a full year in the neoadjuvant [setting] and then extending into adjuvant therapy.

We have not seen the data to know whether patients who did not achieve a pathologic complete response still benefited in terms of long-term, event-free survival by continuing the IO therapy. At least for now, a full year of therapy is going to be the standard.

We also know that that patient would benefit from capecitabine. We've seen that, initially, in the CREATE-X trial and confirmed that capecitabine has at least some benefit in the results of the recently reported ECOG-ACRIN EA1131 trial.

Imagine that she also had genetic testing and she has a BRCA mutation. We need to think about adjuvant PARP inhibitor therapy, which resulted in an 8.8% absolute reduction in the 3-year risk of invasive disease-free recurrence.

When you have that patient, do you continue the IO? Do you add capecitabine or add a PARP inhibitor? Do you try to add all three? How do you sequence those?

We don't have data to give us answers right now. The world is about to get really complicated as we sort through the clinical trial data and try to find the nuances that can help us give patients the greatest benefit that we can give them while respecting that all of these therapies have toxicity.

We don't have the data we need to optimally define therapy. There will undoubtedly be other trials mounted to try to answer those questions. In the short term, we have a situation we haven't faced in patients with triple-negative disease. There are many options but not much data to guide us on how to put them together.

I would welcome your thoughts. How would you treat that patient who got neoadjuvant IO therapy, did not have a pathologic complete response, and has a BRCA mutation? What's your choice for what you're going to do with her? You'll definitely be seeing her sometime in the next several months.

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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