Debu Tripathy, MD, On the Future of Triple Negative Breast Cancer Treatment

March 13, 2020

The breast medical oncologist discussed new treatment options for triple negative breast cancer as new targets become readily available for this aggressive cancer type.

Debu Tripathy, MD, breast medical oncologist at The University of Texas MD Anderson Cancer Center, spoke about the latest updates in the triple negative breast cancer space and the effect they could have for this patient population at the 37th Annual Miami Breast Cancer Conference.


Triple negative breast cancer is one of the more aggressive cancers and traditionally, we've been using chemotherapy really as our only drug. Other targets really haven't revealed themselves as readily. PARP inhibition, as I mentioned earlier, is used in the triple negative cancers that are the subset of them that are related to BRCA 1 or 2 mutations. But in the early stage setting, really chemotherapy is still what we're using. There are trials with neoadjuvant inhibitors of checkpoints, particularly with pembrolizumab (Keytruda), that are showing some promising early results with complete pathologic response. And we're waiting to see if they will impact on disease-free survival.

The other general area that we covered is that when patients receive neoadjuvant treatment for triple negative cancers, as we are increasingly doing now, the presence of residual disease makes a pretty big difference in their outcome and their risk of subsequent recurrence. So, these patients are being looked at for additional therapies. The one treatment that has been used now for the last couple of years is capecitabine (Xeloda) on the basis of the CREATE-X trial, where it did show an improvement in survival. It really showed it in both hormone receptor negative and positive, but the biggest benefit was in the triple negative group of patients. And there are studies now looking at immunotherapy to improve the outcome in these patients. But the results of those trials are not out there still ongoing, in fact.

And the other area that we touched upon at this meeting is how we can monitor these patients. In the past, when patients finished their treatment for early stage cancer, we just, you know, would evaluate them and see them in clinic. We’d continue with screening mammograms just for second cancers, but we really weren't screening them for metastatic disease. We would only work them off if they had symptoms, but it's not conventional practice to use scans. They're not really felt to be that helpful, mostly because they don't detect cancers early enough to be able to do something about it. But with the use of molecular diagnostics and liquid biopsies, where we can measure circulating tumor DNA even at very low levels, there are now methods to look at this in patients with early stage cancer and some early data that shows that if you can start to detect these, that these patients are at much higher risk for recurrence, what we don't know yet is what we can do with the information.

So, there are some studies underway now to look at targeted therapies for these patients or maybe non targeted therapies, for example, the immunoconjugates sacituzumab govitecan, which has some activity in refractory triple negative breast cancer could be used in these patients, or even cytotoxic therapy, or maybe we can just use capecitabine again, but use in a more focused way. So, these are all trial designs that need to be developed and run over time. And then it may be that patients that have specific genomic lesions that can be targeted with things like PI3-kinase inhibitors could be used as well. So that is a wide-open field, I expect more developments in that area as well.

In metastatic triple negative breast cancer, the outcomes are still very poor unfortunately. Patients, some patients do have long responses to chemotherapy and immunotherapy. Immunotherapy now has been approved for about a year now and specifically atezolizumab, but with an add paclitaxel in patients with PD-L1 positive cancers. The future for that particular type of cancer rests in several different areas I would say. One is to still improve upon that first step we've taken with him immunotherapy. Can there be other immune drugs for example, we know in patients that have received chemotherapy there is what's called exhaustion of the immune cells. And these can be reversed with for example, drugs that target LAG-3 which is known to be associated with that phenotype.

There's activators of the immune system, interferon pathway activators innate immunity activators, there’s cell based therapy that's being designed for specific mutations that a patient may harbor looking at their tumor infiltrating lymphocytes or cloning out antigens, that to which they may be sensitive or that may be tumor specific. This is all really at its very early stages, but we hope it moves forward quickly. The area of immunoconjugates is very important. Sacituzumab govitecan is one that's furthest along and is likely to be approved first because we already have data, uncontrolled data, right, phase II data showing activity in that disease with a randomized trial called the ASCENT trial in progress and we'll report soon. And there's other immunoconjugates that are being looked at as well. So that is another area that's growing.


And then finally, the broad area of targeting specific lesions, fibroblasts growth factor receptor, AKT amplification, other mutations. There are trials with PI3 kinase and AKT inhibitors in triple negative cancers that are ongoing or planned. So, the whole genomic targeting area is also being looked at as well.