The initiation of Tumor Treating Fields (TTFields) at the start of chemoradiotherapy did not induce a statistically significant improvement in overall survival (OS) compared with using TTFields in the subsequent maintenance phase in patients with newly diagnosed glioblastoma, missing the primary end point of the phase 3 TRIDENT trial (NCT04471844).1
Top-line findings from the trial showed that in the intention-to-treat population, patients who started TTFields at the beginning of chemoradiotherapy (Early Start Arm) achieved a median OS of 17.7 months vs 17.5 months in those who started TTFields during maintenance (Maintenance Start Arm; HR, 0.953; P = .519).
“TRIDENT represents the largest glioblastoma trial focused on optimizing the integration of TTFields therapy into standard chemoradiotherapy,” Wenyin Shi, MD, PhD, a professor of radiation oncology and co-director of the Jefferson Brain Tumor Center at Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University in Philadelphia, Pennsylvania, stated in a news release. “Although the study did not meet its primary end point, it reaffirmed the clinical value of TTFields therapy and demonstrated promising signals that earlier initiation of TTFields treatment may improve outcomes for selected patients.”
Patients across both arms of the trial experienced durable survival outcomes. In the Early Start Arm, the respective 1-, 2-, and 3-year OS rates were 70.9%, 33.9% and 22.5%; these respective rates were 72.0%, 31.6% and 18.4% in the Maintenance Start Arm.
Additionally, the investigators observed no new safety signals and determined that the early initiation of TTFields was feasible. Device-related safety outcomes were consistent with those from previously conducted clinical trials of TTFields in glioblastoma.
TRIDENT Trial in Glioblastoma: Top-Line Data Takeaways
- The TRIDENT trial missed its primary end point, as initiating TTFields at the start of chemoradiotherapy resulted in a median OS of 17.7 months compared with 17.5 months with initiation during the maintenance phase.
- Despite the lack of statistical significance in the primary end point, the study demonstrated durable OS rates, including a 3-year OS rate of 22.5% for the Early Start Arm vs 18.4% for the Maintenance Start Arm.
- Investigators confirmed that early initiation of TTFields is both feasible and safe, with device-related outcomes consistent with prior trials and no new safety signals observed.
“We are committed to improving the [management] of glioblastoma and are grateful to our investigators and the patients and families who made the TRIDENT trial possible,” Uri Weinberg, MD, PhD, chief medical and innovation officer of Novocure, added in the news release. “The study did not meet its primary end point, but the results from TRIDENT demonstrated the feasibility and safety of initiating TTFields therapy during chemoradiation. We look forward to sharing additional analyses from this trial, which may inform future treatment approaches for patients with specific characteristics.”
The findings from TRIDENT have been accepted for presentation at the 2026 American Society for Radiation Oncology Annual Meeting.
What was the design of the TRIDENT trial in glioblastoma?
This global, multicenter trial enrolled 981 patients (at least 18 years of age outside the US and at least 22 years of age within the US) with newly diagnosed glioblastoma, who were randomly assigned following surgery, including patients who had clinical or radiographic deterioration during chemoradiation.1,2 Patients received either TTFields concomitantly with chemoradiation (consisting of temozolomide and radiation therapy), or TTFields after the completion of chemoradiation. In both arms, TTFields and maintenance temozolomide (Temodar) were intended to be continued after chemoradiation therapy. Across both arms, approximately 25% of patients did not initiate the maintenance phase.
OS served as the primary end point. Secondary end points included progression-free survival (PFS); OS rates at 1, 2, and 3 years; overall response rate; next PFS; 6- and 12-month PFS rates; and the severity and frequency of adverse effects.
What were the characteristics of the patients with glioblastoma who were enrolled in TRIDENT?
Patients had a median age of 60 years.1 The baseline characteristics of the population were balanced between the 2 arms. Across all patients, 38% had a Karnofsky performance score of 70 or 80, 39% had received a methylated MGMT promoter, 5% had IDH-mutant tumors. Regarding the extent of surgical resection, which was also balanced between the arms, 51% of patients had undergone a gross total resection, 37% of patients had undergone a partial resection, and 12% of patients had undergone biopsy only.
References
- Novocure announces topline data from the phase 3 TRIDENT trial evaluating earlier use of tumor treating fields therapy in newly diagnosed glioblastoma. News release. Novocure. June 18, 2026. Accessed June 19, 2026. https://investor.novocure.com/news-releases/news-release-details/novocure-announces-topline-data-phase-3-trident-trial-evaluating
- Pivotal, randomized, open-label study of Optune (Tumor Treating Fields) concomitant with RT & TMZ for the treatment of newly diagnosed GBM (EF-32). ClinicalTrials.gov. Updated March 30, 2026. Accessed June 19, 2026. https://clinicaltrials.gov/study/NCT04471844
