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ASCO 2025 | The emergence of targeted therapies and ICIs for brain metastasis

Manmeet Ahluwalia, MD, MBA, FASCO, Baptist Health South Florida, Miami, FL, provides an overview of the evolving treatment landscape for brain metastasis. There has been a shift from surgery and whole-brain radiation to targeted therapies and immune checkpoint inhibitors (ICIs), which have shown promise in the brain. The next step is to investigate combination therapies, particularly with antibody-drug conjugates and immune checkpoint inhibitors, while also addressing concerns about potential increased radiation toxicity. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.

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Transcript

As a brain metastasis expert, I’ve been exhilarated by the developments we have seen in medical therapies or systemic agents in the last decade or two. Because traditionally, the treatment for patients with brain metastasis was surgery or radiation. And over the last two decades, most of that radiation has now gone to radiosurgery and not whole-brain radiation for most patients...

As a brain metastasis expert, I’ve been exhilarated by the developments we have seen in medical therapies or systemic agents in the last decade or two. Because traditionally, the treatment for patients with brain metastasis was surgery or radiation. And over the last two decades, most of that radiation has now gone to radiosurgery and not whole-brain radiation for most patients. But now we have a plethora of trials and data now showing that both targeted therapies and immune checkpoint inhibitors are very effective in the brain as well compared to the rest of the body. So the next cadre of trials is going to be how do we combine these agents, especially now we have drugs like antibody-drug conjugates, and there’s always this worry and there’s some preliminary data that there could be increased radiation toxicity when you combine antibody-drug conjugates with focused forms of radiation. And similar worry is there for immune checkpoint blockade too. So there are a number of trials which are ongoing right now and we are leading several of those prospectively studying the toxicity because we know these combinations are effective. But the question is, are they more toxic? Because for patients with cancer, it’s almost like how much benefit is our patient going to get and at what cost? So our trials will focus on efficacy but also toxicity.

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