TTFields/SOC Yields Significant Survival Benefit in Metastatic NSCLC

"This is a promising development for a population of patients with limited treatment options. The results suggest that [TTFields] therapy can safely be used along with standard systemic therapies to extend survival without reducing quality of life," according to Ticiana Leal, MD.

Treatment with Tumor Treating Fields (TTFields) and standard therapy resulted in a significant improvement in overall survival (OS) in a population of patients diagnosed with metastatic non­–small cell lung cancer (NSCLC) with disease progression following platinum-based chemotherapy, according to findings from the phase 3 LUNAR study (NCT02973789).¹

The median OS was 13.2 months (95% CI, 10.3-15.5) in the TTFields arm compared with 9.9 months (95% CI, 8.1-11.5) in the standard therapy arm (HR, 0.74; 95% CI, 0.56-0.98; P = .035) with a median follow-up of 10.6 months (IQR, 6.1-33.7) and 9.5 months (IQR, 0.1-32.1) in each respective arm.

The OS rate at 1 year was 60% (95% CI, 47%-71%) among those treated with TTFields/immune checkpoint inhibitor and 46% (95% CI, 33%-57%) among those treated with only an immune checkpoint inhibitor. The corresponding rates were 46% (95% CI, 33%-57%) and 38% (95% CI, 27%-49%) among patients treated with TTFields/docetaxel and docetaxel, respectively.

“The results of the LUNAR trial support the use of [TTFields] therapy in metastatic NSCLC in the second line and beyond,” primary investigator Ticiana Leal, MD, a researcher and medical oncologist at Winship Cancer Institute of Emory University, and associate professor and director of the Thoracic Medical Oncology Program in the Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta, said in a press release on the findings.² “This is a promising development for a population of patients with limited treatment options. The results suggest that [TTFields] therapy can safely be used along with standard systemic therapies to extend survival without reducing quality of life.”

The pivotal, open-label study was conducted at 130 sites across 19 countries in North America, Europe, and Asia. The LUNAR study included patients who had been histologically or cytologically diagnosed with metastatic disease and had radiological progression. Patients also needed to have an ECOG performance status of 0 to 2 and a life expectancy of 3 months or more to enroll on the study.

Patients who enrolled were randomly assigned 1:1 to receive either TTField plus standard therapy or standard therapy alone. Several standard therapy regimens were included in the study:

• 75 mg/m² of intravenous docetaxel every 3 weeks
• 240 mg of intravenous nivolumab (Opdivo) every 2 weeks, 480 mg every 4 weeks, or a body weight–based dose
• 200 mg of intravenous pembrolizumab (Keytruda) every 3 weeks, 400 mg every 6 weeks, or a body weight–based dose
• 840 mg of intravenous atezolizumab (Tecentriq) every 2 weeks, 1200 mg every 3 weeks, and 1680 every 4 weeks

TTFields was administered using continuous delivery at 150 kHz to the thoracic region; the current recommendation is to obtain an average use of at least 75% per day.

The study’s primary outcome was OS, and key secondary end points included progression-free survival (PFS), overall response rate (ORR), OS in select patient subgroups, quality of life, and adverse effects (AEs).

A total of 276 patients enrolled on the study, 137 of whom were in the TTFields cohort, and 139 were in the standard therapy cohort. Patients had a median age of 64 years (IQR, 59-70), and the majority were male (64%). Additionally, most patients were current or former smokers (84%), had nonsquamous histology (57%), and received a single line of systemic therapy (87%).

Ninety-seven percent of patients who were treated with standard therapy received systemic therapy for a median of 12.5 weeks (IQR, 5.1-25.1). Patients were treated with TTFields for a median duration of 14.6 weeks (IQR, 5.3-41.1) when combined with an immune checkpoint inhibitor and 12.7 weeks (IQR, 3.9-22.0) when combined with docetaxel.

Most patients discontinued treatment (98%), with the most common reason being progression or death (61%). A total of 28% of patients received salvage therapy following study treatment discontinuation, with common agents including docetaxel (31%) and gemcitabine (27%).

Thirty-eight patients died in the TTFields/immune checkpoint inhibitor group along with 52 among those treated with immune checkpoint inhibitor alone. Additionally, 54 and 57 patients died in the subgroup of patients treated with TTFields and docetaxel vs docetaxel alone, respectively.

In terms of other outcomes, the ORR was 20.4% (95% CI, 14.0%-28.2%) in those treated with TTFields and standard therapy vs 17.3% (95% CI, 11.4%-24.6%) with standard treatment alone (two-sided P = .50). Five patients who received an immune checkpoint inhibitor achieved a complete response. Moreover, the median PFS was 4.8 months (95% CI, 4.1-5.7) and 4.1 months (95% CI, 3.1-4.6) in each respective arm (HR, 0.85; 95% CI, 0.67-1.11; P = .23).

Ninety-four percent of the study’s overall population experienced at least one AE, including 97% of those in the TTFields-based arm and 91% in the standard therapy alone arm. Additionally, 59% and 56% of patients developed grade 3 to 5 toxicities, respectively. Common toxicities associated with systemic therapies or underlying disease included fatigue (33%), musculoskeletal pain (32%), anemia (23%), dyspnea (23%), diarrhea (19%), and leukopenia (15%). Serious AEs were observed in 53% of patients in the experimental arm compared with 38% of those in the control arm.

References

1. 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. 2023;24(9):1002-1017. doi:10.1016/S1470-2045(23)00344-3
2. Novocure announces The Lancet Oncology publishes primary data from phase 3 LUNAR clinical trial in patients with metastatic non-small cell lung cancer after platinum-based therapies. News release. Novocure. August 29, 2023. https://bit.ly/3YTM5Pb