Explaining Brain Cancer and Metastases Updates for Patients

Experts shared promising updates on brain cancer and metastases, including CATNON trial results and new targeted treatments, during ASCO 2025.

Patients with primary brain tumors and brain metastases received updates on their disease and potential treatment options at the 2025 ASCO Annual Meeting. To best understand the updates, experts Dr. Joshua K. Sabari and Dr. Manmeet Singh Ahluwalia sat down to delve into the key takeaways for these patients from the meeting.

The pair discussed findings from the CATNON trial, as well as reviewed data with HER3-DXd and immunotherapy combinations, highlighting advancements which reflect on the shift toward more targeted and less toxic treatment strategies for this patient population.

Sabari is the editor in chief of CURE. He also serves as an assistant professor in the Department of Medicine at NYU Grossman School of Medicine and director of High Reliability Organization Initiatives at Perlmutter Cancer Center. Ahluwalia is a neuro-oncologist. He serves as the chief scientific officer, chief of medical oncology, deputy director and Fernandez Family Endowed Chair in Cancer Research at Baptist Health Miami Cancer Institute.

Sabari: Hello. I'm Dr Joshua Sabari. I'm a thoracic medical oncologist at NYU Langone Health, Perlmutter Cancer Center in New York. I'm also the editor in chief of CURE.

I'm excited today to be joined by Dr. Ahluwalia, a neurooncologist, who will be discussing key insights and takeaways from ASCO 2025. Dr. Ahluwalia, please introduce yourself.

Ahluwalia: Thank you so much. Dr. Sabari. I'm Manmeet Ahluwalia. I'm a medical oncologist by training. I take care of patients with brain tumors, and I serve as the chief of medical oncology, chief scientific officer, and deputy director of the Miami Cancer Institute.

Sabari: So, Dr. Ahluwalia, give us some of the key takeaways in the central nervous symptom space at ASCO 2025.

Ahluwalia: Sure. ASCO 2025, as usual, was an exciting meeting for us in brain tumors. When we say, "brain tumors," we refer to tumors that originate in the brain, known as primary brain tumors (typically glioblastoma or gliomas), or tumors called brain metastases, which are cancers from other parts of the body that have spread to the brain. The most common cancers that spread to the brain are lung cancer — which you treat, Dr. Sabari — breast cancer, and melanoma.

The one abstract I really wanted to highlight today was the CATNON trial. This was a randomized trial conducted primarily by the EORTC in Europe, with cooperation from U.S. federal cooperative groups including NRG. It was a 750-patient study focusing on grade 3 glioma patients. As we know, glioblastoma is the most common primary malignant brain tumor in the United States, affecting 15,000 patients annually. We also see around 3,500 grade 3 glioma patients.

This trial investigated whether the addition of Temodar (temozolomide), the most common chemotherapy used to treat glioma patients, adds benefit to radiation. Radiation is the foundation of treatment for patients with grade 2, grade 3 and grade 5 gliomas or glioblastomas. So, this trial addressed the question: Can chemotherapy add value to radiation?

Within that, there was a twofold question. First, can we give concurrent chemotherapy? This means administering chemotherapy at the same time as radiation. Typically, radiation for these patients lasts around six weeks. The first question was, could chemotherapy be given concurrently with this radiation? The second question was, can chemotherapy be given adjuvantly? This means administering it after radiation is finished, typically five days every 28 days for 12 months.

What the trial basically showed was that there was benefit from chemotherapy in the adjuvant setting. This means patients can receive radiation for six weeks, then typically get a four-week break, and then receive 12 months of chemotherapy with Temodar. Crucially, there was no additional benefit from giving it concurrently. Why is that important? Because every time we give patients chemotherapy, they do experience side effects.

Although Temodar is a relatively well-tolerated chemotherapy compared to many others we use, it can lead to low platelet counts and low blood counts. We see this in around 10% of patients, sometimes requiring a decrease in the chemotherapy dose. Obviously, in neuro-oncology, like all cancer fields, the primary questions facing physicians when treating patients are: How much will we help our patients, how long will they live with the treatment, and at what cost? So, essentially, this trial showed that these Grade III patients can receive radiation upfront and then get chemotherapy after radiation, and there is no need to give additional concurrent chemotherapy with radiation, which can sometimes lead to increased toxicity or side effects.

I think that was a nice study. It also showed us that molecular profiling is important, and new classifiers are being developed to help us prognosticate, meaning we can figure out which patients are more likely to benefit from a certain chemotherapy compared to those who are less likely. That's the Holy Grail of precision oncology, as we all discuss. This was the abstract that really caught my eye in the primary brain tumor space.

Sabari: Dr. Ahluwalia, can you continue by highlighting some of the top trials presented on treating brain metastases?

Ahluwalia: Now, I'm going to move on to brain metastases, which is a common challenge we face in the clinic every day. Almost 200,000 patients in the United States are diagnosed with brain metastases annually. The three most common cancers that spread to the brain, as I said before, include lung cancer, breast cancer, and melanoma, though rare tumors can also spread to the brain.

I'm going to cover two abstracts today. One was on HER3-DXd (patritumab deruxtecan), a new antibody-drug conjugate. As you know, there's been a lot of excitement in the breast oncology space, especially with a drug called Enhertu fam-trastuzumab deruxtecan-nxki), which is truly transforming outcomes for patients with HER2-positive breast cancer. Similarly, this is an antibody-drug conjugate, which are like "smart bombs." We administer it to patients, it attaches to a protein expressed on the surface of cancer cells, and then the "payload" or chemotherapy is released inside the cancer cells. So, it's truly precision oncology, or what we call "smart chemotherapy," compared to prior chemotherapies where the benefit came from the chemo attacking dividing cells (typically cancer cells), but it could also attack other dividing cells, such as blood cells, leading to low blood counts.

In this trial, presented by Dr. Matthias Preusser and conducted primarily in Europe, they showed that this HER3 antibody-drug conjugate really provided benefit in patients with brain metastases from lung cancer, with a response rate of 30%. This means in 30% of patients, there was a shrinkage of more than 30%, according to the RANO-BM criteria, a special criterion we use for brain tumors, distinct from the RECIST criteria used for the rest of the body. In breast cancer, five out of 21 patients, or 23%, saw shrinkages.

They also studied another group: patients with leptomeningeal disease. As you know, Josh, sometimes when cancer spreads to the brain, it can also involve the lining around the brain, leading to leptomeningeal disease, a very challenging group of patients to treat. Here, what we found with this antibody-drug conjugate, which was pretty exciting, was that at least 65% of our patients (two-thirds) were able to live beyond three months, and 50% of patients showed a benefit beyond six months. This is good, promising early data. So, I would say, be aware of this antibody-drug conjugate; look for more information. It's exciting.

Then, we presented some of our work from SWOG, another cooperative group, where we looked at a combination of Opdivo (nivolumab) and Yervoy (ipilimumab). As we know, immunotherapy has truly transformed outcomes for patients with non-small cell lung cancer and melanoma, not only in systemic disease but also in brain metastases. However, what we don't know is how patients with rare tumors that spread to the brain behave with this combination. As I said, when you add up these rare tumors, they constitute around 20% of cancers we see in the clinic, so it's not a small proportion. This was the DART trial, conducted by SWOG, involving over 700 sites and over 700 patients.

Basically, this trial showed that the combination of Opdivo, an immune checkpoint inhibitor targeting the PD-1 pathway, when combined with Yervoy, which targets the CTLA-4 pathway (a combination known to work well, particularly in melanoma, and also beneficial in select groups of lung cancer patients, as you know), benefited patients with rare tumors, both in the brain and in the rest of the body. The response rates, meaning the shrinkages, were around 10% to 12%, which is not as high as what we've seen in some other tumor types. But the important takeaway message of this study was that the combination of immunotherapy works in the brain as well as in the rest of the body. So, it was nice to see that we now have new drugs working in brain metastases.

We are having exciting options for our patients. Traditionally, as we all know, radiation was the primary way we treated these patients. While radiation controls the tumor, it can sometimes lead to neurocognitive side effects. So, what we are trying to do is explore whether we can use these medical therapies to help our patients with brain metastases.

Sabari: Thank you for your insights. Really exciting to see updates in primary central nervous system tumors, gliomas, as well as in patients with CNS metastases. As you mentioned, these are quite common, and we know that in patients with leptomeningeal disease (disease involving the lining of the brain), [treatment] can be very complex to treat. We are also very excited to see that some of these antibody drug conjugates, these smart bombs, as you mentioned, are having activity in this setting as well.

I want to thank you for joining us and imparting your wisdom. Also thank you to the CURE community, patients and their caregivers for listening. Thank you.

Ahluwalia: Thank you so much for having me.

Transcript has been edited for clarity and conciseness.

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