FDA Approves TTFields for Previously Treated Metastatic NSCLC

The TTFields approval was supported by data from the phase 3 LUNAR trial (NCT02973789), in which investigators evaluated TTFields with standard of care (SOC) immune checkpoint inhibitor (ICI) or docetaxel for metastatic NSCLC that has progressed during or following platinum-based therapy.

The News

The FDA has approved tumor treating fields (TTFields; Optune Lua) in combination with docetaxel or PD-L1 inhibitors for patients with metastatic non–small lung cell cancer (NSCLC) that has progressed during or following platinum-based therapy, according to a press release from the developer, Novocure.¹

Supporting Data

The TTFields approval was supported by data from the phase 3 LUNAR trial (NCT02973789), in which investigators evaluated TTFields with standard of care (SOC) immune checkpoint inhibitor (ICI) or docetaxel for metastatic NSCLC that has progressed during or following platinum-based therapy.

Topline data showed a median overall survival (OS) of 19.0 months (95% CI, 10.6-28.2 months) with TTFields plus PD-L1 inhibitors vs 10.8 months (95% CI, 8.3-17.6) with PD-L1 inhibitors alone (P = .002). Additionally, the median OS was 11.1 months (95% CI, 8.2-13.9) with TTFields/docetaxel vs 8.9 months (95% CI, 6.5-11.3) in those who received docetaxel alone.

Investigators previously published findings from the trial in The Lancet Oncology.²

The phase 3 results revealed significantly prolonged overall survival (OS) withTTFields plusSOC compared with SOC alone; 13.2 months (95% CI, 10.3-15.5) vs 9.9 months (95% CI, 8.1-11.5), respectively, with a minimum follow-up of 12 months (HR, 0.74; 95% CI, 0.56-0.98; P = .035). OS rates following 1 year were 53% (95% CI, 44%-61%) and 42% (95% CI, 33%-50%) in each respective arm. Median follow-up was 10.6 months (IQR, 6.1-33.7) vs 9.5 months (IQR, 0.1-32.1) for TTFields plus SOC and SOC alone, respectively, as of the data cutoff date.

Among patients receivingICIs (n = 134), the median OS was 18.5 months (95% CI, 10.6-30.3) in the TTFields arm vs 10.8 months (95% CI, 8.2-18.4) in the SOC arm (HR, 0.63; 95% CI, 0.41-0.96; P = .03). Among patients in the docetaxel subgroup (n = 142), the median OS was 11.1 months (95% CI, 8.2-14.1) vs 8.7 months (95% CI, 6.3-11.3) in each respective arm(HR, 0.81; 95% CI, 0.55-1.19; P = .28). Furthermore, median progression-free survival (PFS) for the investigational and SOC arms was4.8 months (95% CI, 4.1-5.7) vs 4.1 months (95% CI, 3.1-4.6), respectively (HR, 0.85; 95% CI, 0.67-1.11; P = .23).

The overall response rate was 20.4% (95% CI, 14.0%-28.2%) in the TTFields group vs 17.3% (95% CI, 11.4%-24.6%) in the SOC only group (P = .23). For each respective arm, 4 and 1 complete responses occurred; all occurred with ICI treatment.

Expert Perspective

“There have been a number of important advances in first-line treatment for NSCLC, but this is an aggressive disease, and most patients will develop progression, with limited effective treatment options in second line and beyond," primary investigator Ticiana Leal, MD, associate Professor and director of the Thoracic Oncology Program at the Winship Cancer Institute of Emory University School of Medicine, said in the press release.¹ "The [OS] results we observed with [TTFields] in the LUNAR study mark the first substantial improvement in more than 8 years in this patient population which, when combined with [TTFields'] lack of systemic toxicity, make this a compelling development for many patients and their physicians who need better treatment options for this advanced disease."

Phase 3 LUNAR Study Design

The trial’s primary end point was OS, and it included key secondary end points of PFS and adverse effects (AEs). Eligible patients were those diagnosed with metastatic NSCLC with an ECOG performance status of 0 to 2 who had progressed during or following platinum-based chemotherapy.

Patients were randomly assigned 1:1 to receive either TTFields and SOC (n = 137) or SOC alone (n = 139) from February 2017 to November 2021. Continuous 150 kHz TTFields therapy was delivered until progression, intolerable toxicity, or patient withdrawal of consent.

TTFields treatment consisted of 4 electrically insulated electrode arrays worn on the chest.³ Array layouts varied based on sex, disease burden, and patient body size.

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 bodyweight-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.

For the total analysis set (n = 276), the median patient age was 64 years, and most patients were male (64%), had nonsquamous histology (57%), received 1 previous line of therapy (87%), and had an ECOG performance status of 0 or 1 (96%).

Adverse Effects

Between the investigational and control groups, AE incidence was 97% with TTFields plus SOC vs 91% with SOC alone. TTField-related AE occurrence was 71%, with the majority of AEs reported as grade 1 or 2 local skin irritation such asdermatitis (39%), pruritus (12%), rash (9%), and skin ulcer (8%).

In the safety population for patients who receivedTTFields plus SOC (n = 133) and SOC alone (n = 134), 12% and 14% required dose reductions to standard therapy, with 14% of those in the TTFields arm discontinuing due to toxicity related to device usage.

The FDA previously accepted a premarket approval application (PMA) for TTFields for NSCLC that has progressed following or during platinum-based therapy in January 2024.⁴

References

1. FDA Approves Novocure’s Optune Lua® for the Treatment of Metastatic Non-Small Cell Lung Cancer. News release. Novocure. October 15, 2024. Accessed October 15, 2024. https://www.businesswire.com/news/home/20241015381082/en
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 16, 2024. https://tinyurl.com/2suast7c
4. Novocure announces FDA acceptance of the PMA application for TTFields therapy in non-small cell lung cancer. News release. Novocure. January 18, 2024. Accessed September 17, 2024. http://tinyurl.com/34x673yb