You’re listening to Project Oncology on ReachMD. On this episode, sponsored by Lilly, we’re joined by Dr. Maryam Lustberg, Associate Professor of Medicine at Ohio State University. Dr. Lustberg is here to share some insight into the next wave of targeted therapies for early stage- HER2-positive breast cancer. Let’s hear from her now.
I would like to highlight the exciting area of small molecule HER2 inhibitors including drugs such as neratinib, tucatinib, and the older drug lapatinib. So currently, neratinib, based on the ExteNET study is approved for high-risk, early-stage breast cancer and tucatinib, based on the amazing study results in the metastatic setting with the study HER2CLIMB, is currently being tested as part of the COMPASS study, in early-stage, high-risk, HER2-positive breast cancer. One of excitement about these drugs is that they have better CNS penetration which is an area of high unmet need in HER2-positive breast cancer. So we’re very excited about the potential expanded use of these HER2 small molecule inhibitors. Another area of excitement is centered around antibody drug conjugates. These drugs, more precisely deliver their chemotherapy payload to the areas in the tumor that have the HER2 signal, and they’re the drug trastuzumab deruxtecan, also known as ENHERTU, for example, is approved in the metastatic setting, but is currently being tested in the early-stage HER2-positive breast cancer as part of the DESTINY 5 breast study for high-risk disease that has not achieved a complete pathologic response after standard preoperative HER2-directed therapy.
So, the incorporation and testing of additional HER2 antidrug conjugates in the early-stage setting is currently in progress, and what we anticipate is as these drugs get approved in the metastatic setting, for them to move up to the early-stage breast cancer setting in trials. And then the third area is really selecting more precisely which breast tumors that are HER2 expressing actually may benefit from actually less therapy, or chemotherapy free regimens, or strongly HER2-expressing tumors that have certain favorable features. So, there are emerging studies suggesting that we can, perhaps, carefully select, the more favorable tumors and test them without chemotherapy and still achieve very good anti-tumor efficacy with better tolerability.
So our goals in improving the treatment landscape remain the same as with other types of breast cancer, but our goals are to continue to improve disease outcomes in early-stage HER2-positive breast cancer, reduce CNS metastases, which continues to be often the primary site of recurrence in early-stage breast cancer. So, this is an area of high unmet need, and as we develop these small molecule inhibitors, I think there’s great potential there. The third area is we want to improve quality of life. Patients diagnosed with early-stage breast cancer can live, thankfully, for many years after diagnosis, and the goals of our newer therapies are, can we both have efficacious anti-tumor efficacy, but also improve quality of life? And four, which kind of covers all of these points, which is that we want to deliver a personalized precision medicine, so the patients that need more therapy can get more therapy that is directly improving their outcomes, while maybe patients with more favorable HER2 tumor types may not need as much therapy and can be spared unnecessary therapy. So, I think all of the therapeutics that we talked about in this session are aimed at delivering it on these goals.
This episode of Project Oncology was sponsored by Lilly. To revisit any part of this discussion and to access other episodes in this series, visit ReachMD.com/Project-Oncology, where you can Be Part of the Knowledge. Thanks for listening.