VIDEO: Important areas of future research for triple-negative breast cancer

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In terms of areas of research, there are always novel targets that we're looking for in triple-negative breast cancers or to try to refine some of the areas that we already know about. So an example of refining area where we already have success is a drug called datopotamab. As you know, sacituzumab is already FDA approved for triple negative breast cancers. Sacituzumab is a Trop-2 antibody drug conjugate that uses as as its payload SN-38, which is related tor irinotecan. So to try to make an antibody drug conjugate more effective, obviously, you could use a different target, but you could also use the same target and make it more effective by choosing a chemotherapy that's either more effective or less toxic, or also choosing a linker that is more easily disengaged. So there're, like I said, different pharmacologic ways to improve the efficacy of an antibody drug conjugate, even if you're using the same antibody. So datopotamab is also using a Trop-2 antibody, but instead of using the SM-38 payload, it uses the deruxtecan payload, which has obviously been a payload that's been very successful in breast cancer because it's the payload for trastuzumab deruxtecan. And in clinical trials from metastatic triple-negative breast cancers as a single agent, the response rates have been in the 30 to 35% range for pretreated metastatic triple-negative breast cancers, which is quite high. Even more encouraging has been combinations when used with durvalumab, a PD-L1 inhibitor, in which a response rate in the BEGONIA phase 1b/2 trial was actually 79%, and that was just presented at ESMO last year.

Another interesting target for triple-negative breast cancers is actually looking at the HER3 antibodies. So HER3 is actually expressed quite highly in breast cancer. It's actually about 70% of all breast cancers express HER3. So there actually has been data looking at a drug called patritumab, and this is also using the deruxtecan payload. And this has also showed encouraging activity for both hormone receptor-positive and triple-negative breast cancers. Even though this is a HER3 antibody, these clinical trials have really been focused on HER2-negative cancers that may be HER3-positive. The response rates for metastatic triple-negative breast cancers in a heavily pretreated population was about 23%, so also encouraging. Another area that I think has been generating a lot of interest is looking at androgen receptor blockade. It's well known that there are some triple-negative breast cancers that are androgen receptor-positive as well. And there are many androgen receptor blockers available through the prostate cancer world. So although both bicalutamide and enzalutamide have been studied in breast cancer, and the response rates are fairly modest, there has been some interesting preclinical data that suggests that CDK4/6 inhibitors may prime the cells to respond to androgen receptors. So there are some clinical trials that are looking at this combination to see if they can improve the modest response rates that have been seen thus far with androgen receptor blockade. The main advantage of androgen receptor blockade is it's very well tolerated from the patient's standpoint, and since androgen receptor-positivity is well-known to be seen in triple-negative breast cancer, this does seem to be a very promising area for research.