Case 3: Atezolizumab/Nab-Paclitaxel for Triple Negative Breast Cancer

Tiffany Traina, MD: This patient had a history of a high-risk triple-negative breast cancer about 2 and a half years prior. At the time, with node-positive disease and a large tumor, this is a patient we likely would have treated with pre-operative chemotherapy, anthracycline and taxane-based regimen, for sure.

And the reason for that is that use of a pathologic complete response pathCR could help refine the adjuvant treatment. So if she were to fail the pathCR and remained at higher risk of recurrence, she could have had the opportunity for capecitabine in the adjuvant setting. Here, it seems she received an adjuvant anthracycline and taxane regimen and had gone to surgery directly.

Unfortunately, here we are 2 and a half years later with recurrence of disease, which is exactly the timeframe in which we often will see recurrence of triple-negative breast cancer.

Appropriately, she has had germline genetic testing and was found to be BRCA negative. I think this is a really important biomarker that must be known for our patients because it is actionable with FDA approval of PARP inhibitors for those women who do have germline BRCA mutations.

I think an important factor that is given to us in her story is that her tumor was tested for PD-L1 and found to be positive by the SP142 antibody. And so in this case, with a disease-free interval greater than a year, a PD-L1 positive first-line metastatic triple-negative breast cancer, I turn to the data from the IMpassion130 study, where first-line treatment with nab-paclitaxel and the addition of atezolizumab was shown to improve progression-free survival within the subset of patients who had a PD-L1–positive tumor.

I think that the observation of what appeared to be longer median overall survival in those patients with PD-L1–ؘpositive disease was also quite compelling. Together that led to the FDA approval of atezolizumab just about a year ago, now.

That would be my recommendation for this patient in the first-line setting, PD-L1–positive, metastatic triple-negative breast cancer, to utilize nab-paclitaxel with atezolizumab.

The results from the IMpassion130 were really practice changing, I think, for all of us in our treatment of patients with advanced triple-negative breast cancer. This led to the approval of the first checkpoint inhibitor for the treatment of breast cancer and specifically in triple-negative breast cancer. And the results were quite compelling.

I think what is really critical is it has made PD-L1 testing a necessity for patients with advanced triple-negative breast cancer because PD-L1 positivity by the Ventana SP142 antibody is the companion biomarker to determine benefit from utilization of atezolizumab or not.

The SP142 antibody assay is considered positive in just the proportion of immune cells looked at. This is different than some of the other PD-L1 assays that are out on the market, in terms of definition.

In some of the other assays there is a denominator of a composite score. In this case, you were looking at positivity in the immune cells.

There was a recent presentation by Hope Rugo, MD, FASCO, and colleagues at ESMO [the European Society for Medical Oncology annual meeting] last fall that was an ad hoc analysis of a subset of the patients from IMpassion 130 where tissue was tested for 2 other PD-L1 assays. And I think the takeaway message from that presentation was that while these other assays, perhaps, defined a larger proportion of patients as PD-L1 positive, the predictive biomarker for benefit from adding atezolizumab in IMpassion130 remained the SP142 antibody.

There was good concordance that if you were SP142 positive the tumor was likely to be positive by one of those other assays, but the reverse was not necessarily the case.

So Ventana SP142 percent positivity in immune cells remains the preferred biomarker of choice for predictive value.

I think as oncologists we needed to become much more aware of the potential immune-mediated adverse events when using checkpoint inhibitors. Essentially, inflammation of almost any organ can take place.

In IMpassion130 the immune-related adverse events of interest, if you will, were largely related to hepatitis, with a slight increase, and perhaps the most profound observations were either hyperthyroidism or hypothyroidism. We need to keep in mind the importance of monitoring thyroid function.

Thankfully, in IMpassion130 there did not appear to be an increase in things like adrenal insufficiency. But we need to be aware of the potential for these and be alert to sometimes what may appear to be somewhat nonspecific adverse effects or nonspecific symptoms, and know that we need to be monitoring LFTs [liver function tests] and TFTs [thyroid function tests] on a regular basis.

Transcript edited for clarity.