Residual Disease and HER2-Low Status in Triple-Negative Breast Cancer


Hope S. Rugo, MD, FASCO, and Paolo Tarantino, MD compare treatment approaches for HER2-low and triple-negative breast cancer.


Paolo Tarantino, MD: In terms of biomarkers, what do you think, Hope? What could improve?

Hope S. Rugo, MD, FASCO: Well, so I’ll just go back over some of the things that you went through in nice detail. Right now, the standard of care is to continue pembrolizumab [Keytruda] for the post-neoadjuvant setting. And there are preclinical data that suggests that there may be some interaction. We’ve got a lot of preclinical data that doesn’t pan out but there’s some data that suggests that if you give an ADC [antibody-drug conjugate], you might enhance the efficacy of the checkpoint inhibitor. And then we’ve also seen patients whose cancer didn’t melt away with trastuzumab [Herceptin] or trastuzumab and pertuzumab [Perjeta] who still seem to benefit from ongoing treatment. For example, the metastatic setting patients with HER2-positive disease who don’t have stable disease after their CLEOPATRA trial-like regimen, then continue on antibodies, and we saw this in our biosimilar trial. There are patients who get a better response as they continue. I still think that the standard of care for patients who have a residual disease is to continue the checkpoint inhibitor until we prove otherwise.

This idea of adding in antibody-drug conjugates is hugely appealing and the optimized RD, or residual disease trial, as you pointed out, will study that with sacituzumab govitecan [Trodelvy]. But there’s also the question of who doesn’t need it and that’s optimized PCR [polymerase chain reaction], where patients will be randomized to continue or not. So it’s really important to do that. But I was also fascinated with the SCARLET trial. The SCARLET trial is a cooperative group trial that is based on work from Priyanka Sharma, MD, from the University of Kansas Medical Center in Kansas City, where they will look at a non-anthracycline-based regimen. And you talked about the older, frailer patients, where who knows what the right regimen will be, but showing what patients could get by with docetaxel/carboplatin with pembrolizumab vs the carboplatin/paclitaxel AC [Adriamycin (doxorubicin) plus Cytoxan (cyclophosphamide)]-type regimen, I think is also a really important question that will be hopefully answered by that neoadjuvant trial.

You made a point earlier, Paolo, which I think is worth discussing before we move on to the next step in her disease course, which is that her disease was HER2 1+, and we would call that HER2-low now, as opposed to zero ER/PR negative HER2 1+. You mentioned that we don’t care about PD-L1 in early-stage triple-negative breast cancer and I see it being gotten all the time. We showed definitively now in 2 randomized trials, PD-L1 doesn’t predict benefit from checkpoint inhibitors. Do we care about HER2-low status in the neoadjuvant early-stage setting?

Paolo Tarantino, MD: It is a great question and right now, no, we don’t. Right now, the HER2 IHC [immunohistochemistry] score really doesn’t change our treatment in the early setting. Although, as we will see, it does in the metastatic setting. And the thing is many studies were conducted if HER2-low expression could come from a different prognosis or a different biology. And from what we understand right now, it really doesn’t change the biology and prognosis of these tumors if they are HER2-low or HER2-0. What matters is whether the tumor is HER2-positive or -negative and, of course, your more receptor. So now in terms of treatment decisions, the HER2 score doesn’t matter in this setting. But we will see that instead in the metastatic setting, it can make a large difference.

Hope S. Rugo, MD, FASCO: It’s a really good point. I think that that’s important for us as we’re moving forward. And then now, of course, we want it listed because we might want to know 8 months later if the patient has a recurrent disease.

Transcript edited for clarity.

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