Potential Evolutions in the TNBC Treatment Paradigm
Insights From: Tiffany Traina, MD, Memorial Sloan Kettering Cancer Center
Tiffany Traina, MD: The results of IMpassion130 actually open up many more questions in the management of advanced triple-negative breast cancer. For the 40% of patients who have PD-L1 [programmed death-ligand 1]–positive tumors who may go on to receive first-line nab-paclitaxel [nanoparticle albumin-bound paclitaxel]–atezolizumab, it is unclear what the optimal second-, third-, and further-line therapy should be. Our go-to drugs often are not just taxanes but platinum, and so a remaining question that we hope to see answered with some upcoming trials are with other partner chemotherapy drugs like platinum, such as eribulin. Another clinical question is what to do for our patients who recur within 12 months of their early diagnosis. Those patients would have been excluded from IMpassion130.
A question that I think remains unanswered is how we should manage patients with germline BRCA mutations. We have very compelling data for efficacy with a very manageable adverse event profile with PARP inhibitors. So IMpassion130 cannot answer that for us, neither can the other randomized trials of PARP inhibition alone, but there are ongoing studies to look at partnering PARP inhibition with checkpoint inhibitors. And I think that these are exciting data, but as we try to put this into context of the other active agents, including AKT inhibitors or androgen receptor antagonists, we just do not yet know the optimal sequence for these agents.
I think we have some compelling data hopefully coming soon of other checkpoint inhibitors in combination with platinum and doublet chemotherapy, so that will be interesting to see. These are also in partner with paclitaxel, not just albumin-bound paclitaxel. So that’s worth keeping an eye on. I think the whole idea of moving this approach into earlier lines of therapy—adjuvant and neoadjuvant—will be of interest, when there are small volumes of disease around, to hopefully help see more cure in triple-negative breast cancer.
As I approach the treatment recommendations for a woman with metastatic triple-negative breast cancer, I envision meeting really a platform of data. I now need to know her tumor’s PD-L1 status. I need to know the germline BRCA status. I find it very interesting and important to have next-generation tumor sequencing because that may open up opportunity for other targeted therapies in development. We’ve seen some interesting data from 2 different trials looking at AKT inhibitors in triple-negative breast cancer. So I think having this platform to characterize the triple-negative breast cancer is really important.
Additionally, right now androgen receptor [AR] testing by IHC [immunohistochemistry] is really the testing modality that we have available, but that is hopefully a surrogate for this luminal AR subtype, in which case that opens up even additional avenues for treatment. So at each decision point we need to understand what the signature is of the triple-negative breast cancer to the best of our ability. And recognizing that we always have cytotoxic chemotherapies, I’d like to see that we’re able to have a bit more personalized decision making based on the biology of the disease.
Looking ahead to the next 5 years in triple-negative breast cancer, I think we’ve seen such tremendous progress in the past 5 years, and that is reason to be hopeful. With the IMpassion130 results, we now have our first indication in metastatic triple-negative breast cancer for an immune-directed therapy. And I would be hopeful that we see progress in incorporating those drugs earlier on in the disease course and treatment, such as in the neoadjuvant and adjuvant setting. I would be encouraged to see what different combinations look like for our patients. I think, as I have mentioned, that it’s important to have next-generation sequencing and gather tumor data over time to see how our optimal targeted therapies may change as well.