TTFields Earns Japanese Approval in Unresectable Advanced/Recurrent NSCLC

Those treated with TTFields plus an PD-1/PD-L1 inhibitor or docetaxel achieved a median OS of 13.2 months vs 9.9 months in those not treated with TTFields.

The Japanese Ministry of Health, Labour, and Welfare has approved tumor treating fields (TTFields; Optune Lua®) for concurrent use with PD-1/PD-L1 inhibition in adult patients with unresectable advanced/recurrent non–small cell lung cancer (NSCLC) who have progressed after platinum-based chemotherapy, according to a press release from the drug’s developer, Novocure.1

The ministry’s decision is based on results from the phase 3 LUNAR trial (NCT02973789), in which TTFields was assessed with either standard of care (SOC) immune checkpoint inhibitors (ICIs) or docetaxel for the treatment of the aforementioned population. Findings were previously published in The Lancet Oncology.2

Topline results revealed that the primary end point of overall survival (OS) was met, with TTFields associated with a 3.3-month advantage (P = .04) when used with ICI or docetaxel. Specifically, those treated with TTFields plus an PD-1/PD-L1 inhibitor or docetaxel achieved a median OS of 13.2 months (95% CI, 10.3-15.5) vs 9.9 months (95% CI, 8.2-12.2) in those not treated with TTFields.

Of 2 prespecified powered secondary end points, only 1 met significance. Patients treated with TTFields plus ICI showed a median OS of 19.0 months (95% CI, 10.6-28.2) vs 10.8 months (95% CI, 8.3-17.6) in those treated with an ICI alone, which showed a significant difference of more than 8.0 months (P = .02). Furthermore, those randomly assigned to receive TTFields plus docetaxel had a median OS of 11.1 months (95% CI, 8.2-13.9) vs 8.9 months (95% CI, 6.5-11.3) in those who received docetaxel alone, showing a nonsignificant difference of 2.2 months.

“With the Ministry of Health, Labour, and Welfare approval granted to [TTFields], we now have a new treatment option available to patients with advanced NSCLC,” Tetsuya Mitsudomi, MD, PhD, professor at the Division of Thoracic Surgery, Department of Surgery at Kindai University Faculty of Medicine, and president of Izumi City General Hospital, said in the news release.1 “The Phase 3 LUNAR trial showed that use of [TTFields] resulted in improved [OS] rates without severe [adverse] effects, resulting in a significant benefit for patients with this aggressive disease.”

Adult patients with unresectable advanced/recurrent NSCLC were randomly assigned 1:1 to receive TTFields with SOC (n = 137) or SOC alone (n = 139) from February 2017 to November 2021. Continuous 150 kHz TTFields therapy was delivered to the thoracic region to achieve an average usage of at least 75% of each day with the NovoTTF device system. TTFields treatment consisted of 4 electrically insulated electrode arrays worn on the chest, with array layouts varied based on sex, disease burden, and patient body size.3

Docetaxel was given intravenously at 75 mg/m2 over 1 hour every 3 weeks. ICI dosing varied by agent: intravenous nivolumab (Opdivo) was administered at 240 mg every 2 weeks, 480 mg every 4 weeks, or as a body weight-based dose; pembrolizumab (Keytruda) was administered intravenously at 200 mg every 3 weeks, 400 mg every 6 weeks over 30 minutes, or as a bodyweight-based dose; and atezolizumab (Tecentriq) was delivered via intravenous infusion at 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks over 1 hour.

Those enrolled on trial had a median age of 65 years (range, 22-86), 66% of patients were male, and 96% had an ECOG performance status of 0 to 1. PD-L1 expression was collected from 83% of patients enrolled at US sites and was well-balanced across the 4 cohorts.

The primary end point of the trial was OS. Secondary end points included ICI/docetaxel-specific OS, progression-free survival, and adverse effects (AEs).

Among all patients treated with TTFields, device-related AEs occurred in 63.1% of patients, and primarily consisted of skin-related disorders under the transducer arrays. A total of 4% of these patients experienced a grade 3 skin toxicity requiring a dose interruption. No grade 4 or 5 toxicities emerged with the use of TTFields, and no device-related AEs resulting in death were reported.

The FDA previously approved TTFields in combination with docetaxel or PD-L1 inhibitorsas a treatment for patients with metastatic NSCLC who experienced progression following prior platinum-based therapy in October 2024.4

References

1. Novocure’s Optune Lua® receives approval in Japan for the treatment of unresectable advanced/recurrent non-small cell lung cancer (NSCLC). News release. Novocure. September 15, 2025. Accessed September 15, 2025. https://tinyurl.com/bdfdhepf
2. Leal T, Kotecha R, Ramlau R, et al. Tumor Treating Fields therapy with standard systemic therapy versus standard systemic therapy alone in metastatic non-small-cell lung cancer following progression on or after platinum-based therapy (LUNAR): a randomised, open-label, pivotal phase 3 study. Lancet Oncol. 2023;24(9):1002-1017.
3. Effect of tumor treating fields (TTFields) (150 kHz) concurrent with standard of care therapies for treatment of stage 4 non-small cell lung cancer (NSCLC) following platinum failure (LUNAR). ClinicalTrials.gov. Updated September 28, 2024. Accessed September 15, 2025. https://tinyurl.com/2suast7c
4. FDA Approves Novocure’s Optune Lua® for the Treatment of Metastatic Non-Small Cell Lung Cancer. News release. Novocure. October 15, 2024. Accessed September 15, 2025. https://tinyurl.com/js39pxsd