TRIDENT Trial Finds No Survival Benefit With Earlier Tumor Treating Fields Use

The phase 3 TRIDENT trial (NCT04471844) did not meet its primary end point of overall survival (OS) when Tumor Treating Fields (TTFields) therapy was initiated concomitantly with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma, compared with the standard approach of starting TTFields during the maintenance phase after chemoradiation.¹

In the intent-to-treat population, the median OS was 17.7 months in the concomitant-start arm vs 17.5 months in the maintenance-start arm (P = .519), a difference that did not reach statistical significance.

The TTFields therapy, delivered through the wearable Optune Gio device, is already a guideline-supported component of first-line glioblastoma management on the basis of the phase 3 EF-14 trial (NCT00916409), in which maintenance TTFields added to temozolomide significantly improved OS and progression-free survival (PFS) vs temozolomide alone, supporting its FDA approval in this setting.²

The press release highlighted that glioblastoma remains one of the most difficult solid tumors to treat, with a 5-year survival rate of approximately 5% to 7%, and the rationale for TRIDENT was that beginning electric-field therapy earlier, during chemoradiation rather than waiting for the maintenance phase, might enhance the radiosensitizing and antimitotic effects suggested in preclinical work and extend that survival benefit further.¹

“We are committed to improving the treatment of glioblastoma and are grateful to our investigators and the patients and families who made the TRIDENT trial possible,” said Uri Weinberg, MD, PhD, chief medical and innovation officer at Novocure, in a news release.^¹ “The study did not meet its primary end point, but the results from TRIDENT demonstrated the feasibility and safety of initiating Tumor Treating Fields therapy during chemoradiation. We look forward to sharing additional analyses from this trial, which may inform future treatment approaches for patients with specific characteristics.”

TRIDENT was designed as a global, randomized, open-label phase 3 study comparing TTFields therapy (200 kHz) given concomitantly with radiation therapy and temozolomide against the established maintenance-phase regimen in patients with histologically confirmed, newly diagnosed glioblastoma.³ Eligibility required patients be 18 years or older (22 years or older at US sites), have a life expectancy of at least 3 months, and have a Karnofsky performance status of 70 or higher.The trial enrolled patients following maximal debulking surgery, consistent with the population for which Optune Gio already carries FDA approval in combination with temozolomide.Beyond the primary OS comparison, PFS and safety/tolerability were additional outcomes assessed.

Additional data like the exploratory analyses by patient or tumor characteristics are still to come.

The announcement comes about 4 months after the FDA’s approval of Novocure’s device, marketed as Optune Pax, for use with gemcitabine and nab-paclitaxel in advanced pancreatic cancer.⁴

References

1. Adams B. Novocure device fails to improve brain cancer patients’ survival in phase 3 test. Fierce Biotech. June 18, 2026. Accessed June 19, 2026. https://tinyurl.com/mrx6bu7w

2. Premarket approval (PMA). OPTUNE. October 5, 2015. Accessed June 19, 2026. https://tinyurl.com/2bxf4a9u

3. EF-32 (TRIDENT): pivotal, randomized, open-label study of Optune (tumor treating fields, 200kHz) concomitant with radiation therapy and temozolomide for the treatment of newly diagnosed glioblastoma. ClinicalTrials.gov. Updated February 6, 2026. Accessed June 19, 2026. https://tinyurl.com/mrkj3a69

4. Novocure gets FDA nod for tumor-treating electric fields targeting pancreatic cancer. News release. Novocure. February 17, 2026. Accessed June 19, 2026. https://tinyurl.com/d9t3jw9v