Ahulwalia on Targeting the Blood Brain Barrier With Novel Immunotherapies and Precision Oncology


Manmeet Ahulwalia, MD, MBA, underscores how novel treatment approaches in oncology are proving effective in managing brain metastases.

Brain metastases have historically been associated with dismal outcomes. However, while former treatment approaches were centered around surgery or radiation, in the past decade and a half, investigators have made transformative advances in unlocking the scientific understanding of the genomic drivers behind cancer, according to Manmeet Ahulwalia, MD, MBA. Consequently, the oncology community has made great strides in precision medicine and immunotherapy: 2 approaches which are significantly improving outcomes for patients with brain metastases.

Ahulwalia, the Fernandez Family Foundation Endowed Chair in Cancer Research, Chief of Medical Oncology, and Chief Scientific Officer & Deputy Director, Miami Cancer Institute, Baptist Health South Florida, recently presented on the management of brain and leptomeningeal metastases across tumor types during the 40th Annual CFS. In an interview with Oncology Nursing News®, he underscored how the evolution of treatment directions across tumor types have unlocked promising opportunities to penetrate the blood brain barrier.

Some of the cancers which have a greater tendency to metastasize to the brain include lung cancer, breast cancer, and melanoma. According to Ahulwalia, all of these subtypes have seen tremendous progress in the past 2 decades in terms of treatment options and outcomes According to Ahulwalia, patients with lung cancer and brain metastases in 2010 had, on average, an estimated overall survival of 9 to 12 months . However, today, patients with EGFR-mutant lung cancer which has metastasized to the brain are generally expected to survive an average of 2 to 3 years, and for patients with translocation lung cancer with brain metastases, the average survival has been prolonged to approximately 5 years. Small molecular inhibitors with promising blood brain barrier penetration have played a larger part in boosting survival in this arena.

Moreover, drugs like tucatinib (Tukysa) and, more recently, trastuzumab deruxtecan-nxki (Enhertu), have yielded encouraging results for patients with breast cancer and brain metastases. In the melanoma realm, a mere decade or 2 ago, the average survival was approximately 6 months—today immunotherapy advances are helping these patients achieve survival for nearly 4 or 5 years.

Unfortunately, patients with leptomeningeal disease still face dismal prognoses, Ahulwalia says. The good news is that certain patients with leptomeningeal disease now have promising treatments. For instance, osimertinib (Tagrisso) has shown promising benefit in patients with EGFR-mutant lung cancer, and patients with breast cancer have also experienced promising results with intrathecal based approaches. Ahulwalia expresses hope that the advances being made in this space will continue to ramp up in the coming decades and that new treatment approaches will open doors for patients with brain metastases and leptomeningeal disease.

“There have been transformative changes in the last decade or so, which make people like me extremely excited for our patients [and excited] about the progress that we're going to make in the next decade or two,” he concludes.

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