Enhancing NSCLC Brain Metastasis Treatment With MR-Guided Ultrasound: Manmeet Ahluwalia, MD, MBA, FASCO

Combining magnetic resonance (MR)-guided focused ultrasound with microbubbles and immune checkpoint inhibitors (ICIs) could transform non-small cell lung cancer (NSCLC) treatment by reducing radiation side effects and increasing intracranial response rates, according to Manmeet Ahluwalia, MD, MBA, FASCO, chief of medical oncology, chief scientific officer, and deputy director of the Miami Cancer Institute of Baptist Health South Florida.

These findings were presented at the American Society of Clinical Oncology (ASCO) 2025 meeting as part of the LIMITLESS trial.

This transcript was lightly edited; captions were auto-generated.

Transcript

Can you discuss the value of adding MR-guided focused ultrasound with microbubbles with standard ICI therapy for patients with NCSLC?

Non-small cell lung cancer is the most common cause of brain metastases that we see in clinic. Our trial, LIMITLESS, is looking at combining the MR-guided ultrasound to disrupt the blood brain barrier so we can improve the drug delivery and harness the importance of immune priming. Using this technology along with pembrolizumab and chemotherapies, we typically use pembrolizumab and chemotherapies to treat these patients, but the outcomes of these patients are good, but the intent of this study is to double the response rates that we see with medical therapy alone. One advantage of this combination approach is we can keep the radiosurgery or other forms of radiation that is often used to treat these patients as a backup option. So that's the intent of this trial, is to augment the responses or the efficacy of pembrolizumab along with chemotherapies.

How do you anticipate this therapy might impact overall health care resource utilization in this patient population?

In the last few years, there has been an advent of [the] number of targeted therapies and immunotherapies, which are used to treat patients with brain metastases that have really transformed the outcomes for these patients. The intent of this trial is to augment or improve on those responses that we see alone. One way is to combine these immune checkpoint inhibitors with radiation, which sometimes can lead to side effects like radiation necrosis. Hence, we are using an alternative approach of using the blood brain barrier disruption system to increase the drug delivery to the brain, but also [to] take the advantage of the immune priming impact of blood brain barrier disruption. Between the 2, we hope we will be able to improve the outcomes of our patients and not only help them live longer but also have them have a better quality of life.