In a phase III trial (LUNAR) reported in The Lancet Oncology, Leal et al evaluated the addition of tumor treating fields therapy to standard systemic therapy in patients with metastatic non–small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy.

As stated by the investigators, “…Tumor treating fields are electric fields that disrupt processes critical for cancer cell survival, leading to immunogenic cell death and enhanced antitumor immune response.”

Study Details

In the open-label trial, 276 patients from sites in 19 countries were randomly assigned between February 2017 and November 2021 to receive tumor treating fields therapy with standard therapy (n = 137) or standard therapy alone (n = 139). Standard therapy consisted of investigator’s choice of docetaxel, nivolumab, pembrolizumab, or atezolizumab. Previous platinum-based therapy receipt was required, but there were no restrictions on number or type of previous lines of systemic therapy.

Tumor treating fields therapy at 150 kHz was delivered continuously to the thoracic region with the aim of providing an average of ≥ 18 hours/day device usage. Study treatments were continued until disease progression or unacceptable toxicity. Overall, 57% of patients had nonsquamous NSCLC and 32% had received prior immune checkpoint inhibitors. The primary endpoint was overall survival in the intention-to-treat population.

Overall Survival

Median follow-up was 10.6 months (interquartile range [IQR] = 6.1–33.7 months) in the tumor treating fields 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 tumor treating fields 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%).

Among patients receiving an immune checkpoint inhibitor as standard therapy, median overall survival was 18.5 months (95% CI = 10.6–30.3 months) in the tumor treating fields 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 tumor treating fields 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 tumor treating fields 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 tumor treating fields 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 them, the most commonly received agents were docetaxel (31%) and gemcitabine (27%).

Adverse Events

Among 133 and 134 patients in the safety population, grade ≥ 3 adverse events occurred in 59% of the tumor treating fields group vs 56% of the control group; among all patients, the most common adverse events 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 tumor treating fields therapy discontinued in 14% of patients. Tumor treating fields–related adverse events were reported in 71% of patients; of these, 85% had grade 1 or 2 skin and subcutaneous tissue disorders. Adverse events led to death in 10% vs 8% of patients. A total of three deaths were considered related to standard treatment, due to infection in two and pulmonary hemorrhage in one, with no deaths considered related to tumor treating fields therapy.

The investigators concluded, “[Tumor treating fields] therapy added to standard therapy significantly improved overall survival compared with standard therapy alone in metastatic NSCLC after progression on platinum-based therapy without exacerbating systemic toxicities. These data suggest that [tumor treating fields] therapy is efficacious in metastatic NSCLC and should be considered as a treatment option to manage the disease in this setting.”

Ticiana Leal, MD, of Winship Cancer Institute at Emory University, Atlanta, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Novocure. For full disclosures of the study authors, visit thelancet.com.