PD-L1 Positivity in Triple-Negative Breast Cancer

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EP: 3.Neoadjuvant Therapy Options in Triple-Negative Breast Cancer

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EP: 7.Treatment Approaches for Early Breast Cancer Progression

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EP: 9.PD-L1 Positivity in Triple-Negative Breast Cancer

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Transcript:

Hope S. Rugo, MD, FASCO: If a patient like this is PD-L1 positive, and does or doesn’t have a BRCA1 mutation, what do you do, Paolo? You’re going to start with pembrolizumab and chemotherapy, so how do you choose which chemotherapy partner? Is it based on disease-free interval? What do you do? Pembrolizumab was given for 2 years, so what happens at 2 years? Do you stop, or do you continue the chemotherapy for 2 years? How do you manage those patients?

Paolo Tarantino, MD: KEYNOTE-355 defines the way we treat these patients. This trial allowed either taxanes or carboplatin-gemcitabine combined with pembrolizumab. Similarly to what you do if the patient was PD-L1 negative, if the patient has progressed rapidly and has received prior taxane, you might think of using carboplatin. But for most patients, you might instead use a taxane, which is usually preferred in this setting. You would use it until the maximum activity and tolerability from the patient, but then you’d drop the chemotherapy and maintain pembrolizumab instead.

I can’t say I’ve already found myself in the position of having a patient receive pembrolizumab for 2 years after induction, but that’s a great question. It’s a pan-tumor question. Physicians treating melanoma, lung cancer, or other diseases are faced with the question of whether to drop immunotherapy at a certain point. If the patient achieves a deep complete response to the immunotherapy, that might mean that the immune response was long lasting. Some of these patients may be cured from their metastatic disease, but for most other patients, with a stable disease or partial response, I wouldn’t feel comfortable removing the immunotherapy. How would you feel about this?

Hope S. Rugo, MD, FASCO: I don’t feel comfortable removing the immunotherapy either. That’s part of the big issue that we have. You’ve had this nice response, and we’ve seen the data from KEYNOTE-355, so what do you do in that situation? It’s interesting. We’ve had patients on the KEYNOTE-086 trial who got pembrolizumab alone, and we saw low response rates in the second-line and greater setting, even in PD-L1 positive disease. One of those patients was my patient, and she had lung metastases that resolved. But when it got to 2 years, I was too nervous to stop. I had to stop the study therapy and put her on compassionate use. We did eventually stop because she developed bad colitis at 4½ years or so. She’s still NED [no evidence of disease] 3 years later, so we can stop.

In other cancers, patients have been re-treated with residual disease. In breast cancer, we continue to trust trastuzumab and pertuzumab for 10 years or longer. It’s still a remaining question about what to do in these patients. The standard is to stop at 2 years. But I haven’t done that with the atezolizumab and compassionate-use patients, so I’m a little hesitant to stop with pembrolizumab too.

Transcript edited for clarity.