ROADS Phase 3 Data Published in JCO Support GammaTile as Standard-of-Care Option in Newly Diagnosed Operable Brain Metastases
Key Insights
ROADS randomized 230 patients with operable brain metastases (search) across 32 centers to resection plus GammaTile (search) or resection followed by post-operative stereotactic radiation therapy.
GammaTile (search) cut 12-month surgical bed recurrence to 1.3% versus 15.4% with standard of care, with median overall survival of 42.5 versus 17.6 months.
Grade 3 or higher treatment-related side effects were comparable between arms at 20.0% for GammaTile (search) and 21.7% for standard of care.
Results from the randomized, multicenter ROADS trial (NCT04365374) have been published as a Rapid Communication in the Journal of Clinical Oncology, the official journal of the American Society of Clinical Oncology. The trial authors conclude that GammaTile (search), a cesium-131 collagen tile-based radiation therapy (TBRT), should be considered a standard-of-care option for patients with newly diagnosed brain metastases (search).
Rapid Communication is a discretionary designation JCO editors may grant to accepted manuscripts, reserved for findings of exceptional significance. Recommended manuscripts post online within days of acceptance and are openly accessible upon publication, ahead of standard timelines, so that practice-changing data reaches oncologists faster.
Trial Design and Population
ROADS randomized 230 patients with operable brain metastases (search) across 32 centers to treatment with resection plus GammaTile (search) or the standard-of-care approach of resection followed by post-operative stereotactic radiation therapy (SRT). The study authors note that ROADS is a multicenter randomized phase 3 trial with longer median follow-up than the studies that established post-operative SRT as standard of care.
Co-Primary Endpoint Results
GammaTile (search) demonstrated a lower 12-month cumulative incidence of surgical bed recurrence (SBR) compared with standard of care, 1.3% versus 15.4% (HR: 0.07, 95% CI: 0.01-0.56; p=0.012). Expressed as local tumor control, this corresponds to 98.7% at 12 months for GammaTile versus 84.6% for standard of care. The company states this represents the lowest tumor recurrence rate reported in a published randomized controlled trial of newly diagnosed operable brain metastases (search).
GammaTile (search) also reduced the combined risk of tumor recurrence or death by more than 50% compared with standard of care (HR: 0.48, 95% CI: 0.30-0.76, p=0.002).
Overall Survival and Safety
Median overall survival for patients who received GammaTile (search) was more than twice as long as for those who received standard of care, 42.5 months versus 17.6 months (HR: 0.59, 95% CI: 0.37-0.96, p=0.032).
Rates of grade 3 or higher treatment-related side effects remained low and comparable between arms, 20.0% with GammaTile (search) versus 21.7% with standard of care. Functional status, quality of life, time to distant brain failure, adverse events, leptomeningeal disease, and radiation necrosis were similar in both arms. In an exploratory composite analysis, GammaTile reduced the combined risk of tumor recurrence or radiation necrosis by more than 70% compared with standard of care (HR: 0.28, 95% CI: 0.12-0.66, p=0.004).
Addressing the Gap Between Surgery and Radiation
GammaTile (search) is an FDA-cleared, bioabsorbable collagen implant embedded with four cesium-131 radiation sources, placed directly in the surgical cavity at the time of tumor removal. Radiation begins immediately when surgery ends. The current standard-of-care approach for operable brain metastases (search) is surgery followed by post-operative SRT multiple weeks later, once the patient has recovered from surgery. That interval creates a window in which tumor cells left behind after surgery may regrow before radiation begins.
In ROADS, 17.8% of patients randomized to standard of care did not receive their prescribed post-operative SRT, consistent with published data showing that 20-27% of patients do not complete their full prescribed course of post-operative SRT. Because GammaTile (search) is placed at the time of surgery, radiation begins immediately, eliminating the risk of prescribed radiation going undelivered.
The study authors also examined outcomes limited to patients in each arm who received their prescribed radiation. GammaTile (search)'s superiority in local tumor control and surgical bed recurrence-free survival persisted in that comparison.
"That many patients do not receive post operative SRT appears to be an underappreciated issue amongst physicians caring for these patients, but the benefit of TBRT (GammaTile (search)) is not solely increased treatment completion," said Thomas H. Beckham, MD, PhD, Associate Professor of CNS Radiation Oncology at The University of Texas MD Anderson Cancer Center and corresponding author on the publication. "The trial was designed to compare resection and TBRT versus resection and post-operative SRT, a pathway in which some patients do not ultimately receive their planned radiation. But even when we analyzed only those patients in each arm who did receive their assigned radiation, TBRT remained superior on both co-primary endpoints. That tells us this advantage isn't explained solely by guaranteed radiation delivery. TBRT immediately begins concentrating a higher therapeutic dose of radiation right at the resection cavity, providing a continuous dose over the next few weeks, while minimizing radiation to surrounding healthy brain tissue, a fundamentally different biological approach than a delayed course of radiation delivered from outside the body."
Investigator and Company Perspective
"The Rapid Communication publication in the Journal of Clinical Oncology reflects how significant these findings are for patients with newly diagnosed brain metastases (search)," said Jeffrey Weinberg, MD, professor of Neurosurgery at The University of Texas MD Anderson Cancer Center, co-lead investigator of the ROADS trial, and first author on the publication. "Standard-of-care treatment for this disease has always focused on controlling the tumor in the brain so patients can get back to fighting their primary cancer, and TBRT (GammaTile (search)) does that more effectively than existing treatment options. By initiating radiation at the moment of surgery, TBRT closes the gap between resection and radiation treatment for the operable tumor entirely, and this randomized evidence supports it as a new standard-of-care option that gives patients that certainty from day one."
"The data from this multi-institutional randomized trial provide a high level of evidence demonstrating the superiority of resection plus GammaTile (search) over the current standard-of-care. We expect that this rigorous peer-reviewed publication will give physicians confidence in adopting GammaTile as a first-line treatment for patients with newly diagnosed surgical brain metastases (search)," said Dr. Michael Garcia, MD, MS, Chief Medical Officer of GT Medical Technologies. "Broader adoption of GammaTile can enable more patients to live longer without recurrence, an important advance in this indication."
"As a company founded by brain tumor specialists, GT Medical recognizes the importance of randomized, controlled studies in driving the evolution of clinical practice," said Per Langoe, Chief Executive Officer of GT Medical Technologies. "The publication of the ROADS trial results is a key milestone for the company, the clinical community, and patients with newly diagnosed brain metastases (search). We are committed to generating robust evidence in additional brain tumor indications, such as through the ongoing BRIDGES Phase 3 trial for newly diagnosed glioblastoma (search) and providing additional data to inform clinical decision-making."
Device Characteristics and Availability
Each GammaTile (search) is about the size of a postage stamp (2 cm x 2 cm) and contains purposefully spaced seeds containing cesium-131 that emit low-dose rate radiation over several weeks. The tile lines the cavity that remains after tumor removal, distributing radiation across the surface of the cavity and targeting remaining tumor cells when they are at their lowest levels. The emitted radiation travels only a short distance, which maximizes dosing to the tumor cavity while minimizing dose to surrounding healthy brain tissue.
GammaTile (search) is FDA-cleared for newly diagnosed malignant and recurrent brain tumors and has been adopted by more than 150 centers across the United States.