One problem is the progression of brain metastases in patients who have already received radiation therapy and cannot do it again.

The longer these patients live, the higher chance they will develop brain metastases at some point. Dr Criscitiello?Ĭarmen Criscitiello, MD, PhD: We have performed a big part of the process with these new drugs, but there is still an unmet need in treating patients with brain metastases. The data you’re referring to are hypothesis generating, to look in that space and hopefully change the natural history of HER2+ metastatic disease. You can envision in the highest-risk population in early stage disease who failed pathCR, if you had evidence that the combination with tucatinib could prevent the development of brain metastases, that would be an answer to a huge unmet need. I’d love to see those studies, Dr Criscitiello mentioned a combination with T-DM1.

Traina, MD: That’s a generating hypothesis for moving tucatinib, as the TKI that crosses the blood-brain barrier, early into the treatment algorithm. That’s one of the other wishes we have, we believe this combination might help prevent the occurrence of new brain metastases. We need to focus not only on treated patients who have been locally pretreated, but also prevention. Half of the patients who have HER2-positive metastatic disease will develop brain metastases, so we urgently need strategies to prevent this. That’s something we have not addressed yet. It appears that the more active combination of tucatinib, trastuzumab, and capecitabine can prevent the occurrence of brain metastases. Volkmar Müller, MD, PhD: Returning to brain mets, we saw retrospective data of patients who did not have brain metastases at initial diagnosis and entry into the trial.

Thebrain 8 vs thebrain 9