In a phase III trial (LUNAR) reported in The Lancet Oncology, Ticiana Leal, MD, Winship Cancer Institute at Emory University, and colleagues found that the addition of Tumor Treating Fields (TTFields) therapy to standard systemic therapy improved overall survival in patients with metastatic non-small lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.1 Overall survival benefit was greater when TTFields therapy was combined with immune checkpoint inhibitors (ICIs) as standard treatment.
Ticiana Leal, MD
As stated by the investigators, “…TTFields are electric fields that disrupt processes critical for cancer cell survival, leading to immunogenic cell death and enhanced antitumour immune response.”
In the open-label trial, 276 patients from sites in 19 countries were randomly assigned between February 2017 and November 2021 to receive TTFields therapy with standard therapy (n = 137) or standard therapy alone (n=139). Previous platinum-based therapy was required, but there were no restrictions on number or type of previous lines of systemic therapy.
Standard therapy consisted of investigator choice of ICI therapy with nivolumab, pembrolizumab, or atezolizumab (n = 66 in TTFields group, n = 68 in control group) or docetaxel (n = 71 in both TTFields group and control group). Nivolumab was given at 240 mg every 2 weeks or 480 mg every 4 weeks (or at bodyweight-based dose); pembrolizumab at 200 mg every 3 weeks or 400 mg every 6 weeks (or at a bodyweight-based dose); atezolizumab at 840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks; and docetaxel at 75 mg/m2 every 3 weeks. TTFields therapy at 150 kHz was delivered continuously to the thoracic region using the NovoTTF device system with the aim of providing an average of ≥ 18 hours/day device usage. Study treatments were continued until progression or unacceptable toxicity. Overall, 57% of patients had nonsquamous NSCLC and 32% had received prior ICI therapy. The primary endpoint was overall survival in the intention-to-treat population.
The median duration of TTFields therapy was 14.6 weeks with an ICI and 12.7 weeks with docetaxel. Median follow-up was 10.6 months (interquartile range [IQR] = 6.1-33.7 months) in the TTFields therapy group and 9.5 months (IQR = 0.1-32.1 months) in the control group. Median overall survival was 13.2 months (95% confidence interval [CI] = 10.3-15.5 months) in the TTFields therapy group vs 9.9 months (95% CI = 8.1-11.5 months) in the control group (hazard ratio [HR] = 0.74, 95% CI = 0.56-0.98, P = .035). The 1-year overall survival rate was 53% (95% CI = 44%-61%) vs 42% (95% CI = 33%-50%).
Outcomes According to Standard Therapy
Among patients receiving an ICI as standard therapy, median overall survival was 18.5 months (95% CI = 10.6-30.3 months) in the TTFields group vs 10.8 months (95% CI = 8.2-18.4 months) in the control group (HR = 0.63, 95% CI = 0.41-0.96, P = .030), with 1-year rates of 60% vs 46%. Among patients receiving docetaxel as standard therapy, median overall survival was 11.1 months (95% CI = 8.2-14.1 months) in the TTFields group vs 8.7 months (95% CI = 6.3-11.3 months) in the control group (HR = 0.81, 95% CI = 0.55-1.19, P = .28), with 1-year rates of 46% vs 38%.
Among patients with nonsquamous NSCLC, median overall survival was 12.6 months (95% CI = 8.8-19.8 months) in the TTFields group vs 9.9 months (95% CI = 6.9-16.4 months) in the control group (HR = 0.80, 95% CI = 0.54-1.16, P = .28). Among patients with squamous NSCLC, median overall survival was 13.9 months (95% CI = 9.7-17.1 months) in the TTFields group vs 10.1 months (95% CI = 8.3-14.3 months) in the control group (HR = 0.67, 95% CI = 0.44-1.01, P = .050).
A total of 28% of all patients received salvage systemic therapy after disease progression; among these, the most common were docetaxel (31%) and gemcitabine (27%).
Among 133 and 134 patients in the safety population, grade ≥ 3 adverse events occurred in 59% of the TTFields group vs 56% of the control group; among all patients, the most common were leukopenia (14%), pneumonia (10%), and anemia (8%).Serious adverse events occurred in 53% vs 38% of patients. Adverse events led to treatment discontinuation in 36% vs 20% of patients, with TTFields therapy discontinued in 14% of patents. TTFields-related adverse events were reported in 71% of patients; of these, 85% had grade 1-2 skin and subcutaneous tissue disorders. Adverse events led to death in 10% vs 8% of patients. A total of 3 deaths were considered related to standard treatment, due to infection in 2 and pulmonary hemorrhage in 1, with no deaths considered related to TTFields therapy.
The investigators concluded: “TTFields therapy added to standard therapy significantly improved overall survival compared with standard therapy alone in metastatic non-small-cell lung cancer after progression on platinum-based therapy without exacerbating systemic toxicities. These data suggest that TTFields therapy is efficacious in metastatic non-small-cell lung cancer and should be considered as a treatment option to manage the disease in this setting.”
DISCLOSURE: The study was funded by Novocure. Dr. Leal has received support toward this manuscript from Novocure; institutional grants or contracts from Advaxis and Pfizer; consulting fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Blueprint, Daiichi Sankyo, Eisai, Eli Lilly, EMD Serono, Genentech, Janssen, Jazz Pharmaceuticals, Merck, Mirati, Novocure, Regeneron, Roche, and Takeda; honoraria from Aptitude Health, ASTRO, Bioascend, Cardinal Health, Curio, GRACE, I3 Health, IDEO, Larvol, Medscape, Peerview Institute for Medical Education, OncLive, Opinions in Lung Cancer, Society for Immunotherapy of Cancer, Targeted Oncology, UpToDate, and Vindico; and reported board participation or a leadership position for the National Cancer Institute and Georgia Society of Clinical Oncology.
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. Lancet Oncol 24:1002-1017, 2023.