Early Data Shows Potential of Surgically Targeted Radiation Therapy in GBM

Surgically targeted radiation therapy (STaRT) in patients with recurrent glioblastoma (GBM) demonstrated feasibility and safety, according to early data from a prospective multi-institutional observational study (NCT04427384).¹

Findings from the trial were presented at the 2023 ASCO Annual Meeting and showed that at a median follow-up of 5.2 months (range, 0.6-23.2), there were 7 attributed adverse events (AEs) seen in 13% of patients. These AEs were all grade 3 and included chronic fatigue syndrome leaks (n = 2), seizures (n = 2), and cerebral edema, pseudomeningocele, and left hemiparesis (n = 1 each).

Excluding 1 AE, all were coded as related to both radiation and surgery. Further, the patient who had pseudomeningocele experienced a seizure at 47 days. This was considered to be related to radiation alone.

In the study, patients with recurrent GBM were included if they underwent maximum safe resection and permanent implantation of the device(s). A total of 45 patients with recurrent GBM were enrolled for STaRT. Additionally, 2 patients had 2 sites treated, creating a total of 47 implants.

Among those included in the study, 67% of patients were treated at the first recurrence, 24% at the second recurrence, and 13% at the third recurrence, respectively. The median age of patients was 61 (range, 28-75) and 36% of patients were female. Eighty-five percent of patients received prior same-site radiotherapy and the median time from last radiotherapy to implantation was 14.6 months (range, 3.5-57).

In an interview with Targeted OncologyTM, Ahmad Ozair, MBBS, postdoctoral research fellow in neuro-oncology at Miami Cancer Institute, Baptist Health South Florida, discussed treatments for GBM and a trial evaluating STaRT in this patient population.

Targeted Oncology: What does the current treatment landscape for patients with glioblastoma include?

Ozair: Glioblastoma is the most common and the most aggressive primary brain tumor. Unfortunately, the treatment landscape has not evolved so far. Compared with lung cancer where several strides have been made, currently for a newly-diagnosed patient, the patient undergoes surgery, followed by radiation, and chemotherapy. The chemotherapy is in the form of temozolomide, which is done concurrently with radiation, and after radiation as well. The patient continues this treatment strategy until the inevitable recurrence or progression occurs. Typically, the overall survival is between 14-18 months, despite all the advancements made and the treatments given so far.

How have treatments for these patients changed over the past few years?

Over the past few years, a few advancements have been made, but even then, taken together, they only advanced survival by a few months. Chief among them has been bevacizumab [Avastin]. This is a vascular endothelial growth factor inhibitor that is given in the recurrent setting and enhances the quality-of-life and survival by a few weeks to months. The other treatment advancement that has occurred in the last 10 years has been tumor treating fields. These are a novel form of therapy. This is a biomedical device which the patient wears over their head and it is recommended the patient wears them for 18 hours or more on their head. What this does is it interrupts tumor cell division, and tumor treating fields are indicated in both the newly-diagnosed and in the recurrent setting.

Can you discuss your research on STaRT in patients with glioblastoma?

[At ASCO 2023], we presented the initial outcomes from the North American prospective multicenter registry. STaRT is basically an FDA-approved biomedical device, commonly known as GammaTile. GammaTile is a small collegian wafer that is implanted in the resection cavity after the surgeon has taken out the tumors. It is FDA-approved for both newly-diagnosed and recurrent intracranial neoplasms, including glioblastoma. In our study, we studied the initial safety of STaRT for recurrent glioblastoma.

What were the initial outcomes of the study?

In our [prospective multi-institutional observational study] of data from across North America, we had 14 sites and enrolled 45 patients so far, until January 2023. We found that just 13% of the patients had attributable adverse events. All of these patients had grade 3 adverse events, and all of these adverse events were attributed to both radiation surgery except 1 pseudomeningocele. These data made us realize that that as previously studied in prior trials, GammaTile is safe.

What are the main takeaways of this research and what unmet needs still exist in the space?

The main takeaways of this study are that GammaTile therapy for recurrent glioblastoma is safe and feasible. In our study, just 1 patient had cerebral edema out of the 45 patients, which is typically the most common scenario faced by a radiation oncologist when giving radiation to the brain. These data also have prompted the sponsor to initiate a prospective randomized control trial that is due to start in 2023, comparing maximal surgical resection with adjuvant systemic therapy with maximum surgical resection with adjuvant systemic therapy with GammaTile therapy.

The primary unmet need that exists so far is that most of the trials in neurooncology have failed. Amongst those that have succeeded, taken together, they only advanced survival by a few months. We desperately need novel and breakthrough treatments for glioblastoma.

REFERENCE:

Ozair A, Brachman D, Campbell L, et al. Surgically targeted radiation therapy (STaRT) for recurrent glioblastoma: Initial outcomes from a prospective multicenter registry. J Clin Oncol. 2023;41(suppl 16): 2038. doi:10.1200/JCO.2023.41.16_suppl.2038