Evolving Concepts in Treatment for Advanced Breast Cancer - Episode 12
Joyce A. O’Shaughnessy, MD: Let’s transition to the metastatic setting now, and we have another new FDA approval to work into our practice. Tell us about immunotherapy for triple-negative breast cancer.
Aditya Bardia, MD, MPH: In 2018, immunotherapy finally arrived in breast cancer. We have been waiting for immunotherapy for a while, and atezolizumab [Tecentriq] got FDA approved for patients with metastatic triple-negative breast cancer. But interestingly, it was for the subset of triple-negative breast cancer that also has PD-1 expression. It was PD-1 positive, triple-negative breast cancer. This is based on the IMpassion130 trial, which randomized patients to Abraxane [paclitaxel] versus Abraxane plus Atezo [atezolizumab].
In the combination arm, there was an improvement in progression-free survival plus an improvement in overall survival in the PD-1 subgroup. We saw updated results presented at ASCO’s [American Society of Clinical Oncology] Annual Meeting 2019 this year, and essentially in the overall study population, there was no difference in overall survival between the combination group as compared to the Abraxane group alone. But if you look at the PD-1 positive group, that is where you saw an improvement in overall survival. So clinically, we would be using Atezo in patients who have PD-1—positive triple-negative breast cancer.
But a challenge is, how do you define a tumor that is PD-1 positive? What assay do you use, and what’s the concordance of PD-1 positivity between different pathologists? I would argue even between different specimens that someone with metastatic breast cancer might have.
As a recent anecdote, I had a patient who had a PD-1 tumor that was negative in the metastatic specimen. We then tested the primary breast cancer specimen, and that specimen was PD-1 positive. From a patient perspective, if we had just tested the liver specimen, she would not have received access to Atezo, but by testing the primary breast cancer specimen, now she can have access to Atezo. Whether she’ll derive benefit from the drug, we don’t know. But it just begs the question in terms of what specimen to use and what assay to use.
Joyce A. O’Shaughnessy, MD: Yeah. They found that as well in IMpassion130 looking at the percentage that were positive. It was higher in the primary breast cancer than in the metastatic. So of course, I’m in search now of the positives. That’s my goal. I want to send them to the pathology lab that gives me the most positive, and we’re going to check the primary. That’s what I’m doing. But tell us about the testing there Sara, what was actually utilized so that now we’re going to be using that in practice.
Sara A. Hurvitz, MD: I’d first like to talk a little bit about the design of the study and the way they interpreted it. Because the interpretation was that they met the overall survival endpoint because PD-L1—positive patients did derive an overall survival benefit from the addition of atezolizumab. However, the way that the steps were required in reaching that conclusion and doing that analysis of overall survival in PD-L1–positive patients wasn’t totally followed. They should have first tested it in the overall population and then if it was positive, go on to the PD-L1-positive population.
I’m being a stickler, but that’s the way the study was prospectively designed. That said, the FDA did see this is an important finding in an area of high unmet need, triple-negative breast cancer. We have really nothing but chemotherapy, or PARP [poly (ADP-ribose) polymerase] inhibitors if they carry a BRCA mutation. I think they still took that overall survival data, approved it for those patients with PD-L1—positive tumors, and also had a companion diagnostic, which is recommended to be used to determine eligibility using the SP142 antibody, which when I did a poll of colleagues around the country, it’s the minority of academic centers. I would say it would be rare for a community center to have this.
We’re all having to send out this assay on our tumor tissue, which is adding a lot of time, and I have yet to find a triple-negative patient who’s positive. I haven’t been able to utilize Atezo since approval. I’m wondering if it’s this difference in primary and metastatic sample. I’m really hungry for biomarker data to tell us which is more important. Does it matter which one’s positive in terms of determining outcome? There’s a lot of unaddressed questions. But I’m eager to use it; it’s just hard getting there.
Joyce A. O’Shaughnessy, MD: Right. What matters is the 1% or more of infiltrating immune cells is positive, not the tumor cells being positive. I’ve seen some variation among laboratories. Of course, I’m using the one that’s giving the most positive, that’s good.
Transcript Edited for Clarity