Breast Cancer Update, Issue 2, 2016 (Video Program) - Video 21Immune checkpoint inhibitors in triple-negative breast cancer
3:32 minutes.
TRANSCRIPTION:
DR SLEDGE: We have small data sets, I think we’d say, to date. Most of the data that we have to date is in patients with triple-negative breast cancer. Most of that data would suggest that there are, indeed, responders. The response rates to date are somewhere in the 15% to 20% range overall. What we don’t have is the long-term follow-up that we’ve seen in melanoma or non-small cell lung cancer, to see to what extent we have a tail of the curve, because, of course, the exciting part of this in melanoma and non-small cell lung cancer is the existence of patients who are now 5 years out or, in some cases with CTLA-4 agents, 10 years out, where there appears to be a true plateau to the curve. It’s reasonable to think that triple-negative breast cancer might be a good population for checkpoint inhibitors, such as anti-PD-1 drugs. These are the cancers that have the highest mutational load and, therefore, would be expected to have the most neoantigens or neoepitopes that would represent juicy targets for the immune system, if we just super-charge the immune system a little bit with an anti-PD-1 drug. So I think we’re all hopeful that we’re going to see that. Having said that, I think we also have enough data in already to say that this is not going to be a treatment for all triple-negative breast cancers. Now, the truly fascinating data, to me — and it’s very preliminary — has been the combination of taxane-based chemotherapy with nab paclitaxel with checkpoint inhibitor therapy where, in a very small data set we saw a very high response rate with something like 8 out of 9 patients responding. Now, one doesn’t want to make too much out of such tiny data sets. But if that holds true in larger data sets, then looking at combinatorial therapy I think is going to be a very exciting option here. DR LOVE: All of us got a huge surprise about a year and a half ago when instantly we found out that Hodgkin lymphoma was extremely sensitive. Where does this fit in with lung cancer and melanoma? It turns out there really is a biology there in terms of particularly PD-1 expression. What about breast cancer and, also, the various subtypes? For example, do we know what PD-1 expression is on triple-negative versus ER-positive versus HER2-positive, et cetera? DR SLEDGE: I don’t think it’s been as well studied. The data I’ve seen have said that it’s somewhat more common in triple-negative breast cancers. It is absolutely the case that tumor infiltrating lymphocytes are more common in triple-negative breast cancers. And even within triple-negative breast cancers, there are subsets of triple-negative breast cancer where there’s higher rates of lymphocytic infiltration, such as patients who have a BRCA1 mutation. We belong to a same age category. So you’ll remember when we used to call many of these cancers medullary cancers of the breast with a strong lymphocytic infiltrate. It was always the paradox of a population of triple-negative breast cancers that had a really good prognosis. And looking at that through the retrospectoscope, it’s likely that what we were dealing with is exactly this, a strong lymphocytic infiltrate in response to a high neoantigen load. |