Surprising Results With Tumor-Treating Fields (TTF) Electrical Therapy in Lung Cancer

Lung cancer remains the most common cause of cancer-related death worldwide, making the development of effective treatments particularly important. Tumor-treating fields (TTF) therapy is a technology developed by Novocure and approved by the FDA (US Food and Drug Administration). It previously received approval for glioblastoma multiforme (GBM) and FDA approval for mesothelioma . The technology is now being evaluated as a treatment option for patients with metastatic (stage 4) non-small cell lung cancer (NSCLC). This study aims to evaluate how effective TTF therapy is in NSCLC.

The LUNAR Study

In September 2023, Lancet Oncology published LUNAR, a phase III clinical trial evaluating the addition of tumor-treating fields therapy to standard systemic treatment in patients with metastatic non-small cell lung cancer (NSCLC) whose disease had progressed after platinum-based chemotherapy.

A total of 276 patients from 19 countries participated between 2017 and 2021. They were divided into two groups:

• The first group (137 people) received standard treatment alone.
• The second group (139 people) received tumor-treating fields therapy in addition to standard treatment.

For standard treatment, the researchers selected one of four drugs: docetaxel, nivolumab, pembrolizumab or atezolizumab. Participants were required to have received prior platinum-based treatment, but there were no restrictions on the type or number of previous treatments.

Tumor-treating fields therapy was delivered continuously at 150 kHz for at least 18 hours a day, targeting the lung region. Treatment continued until disease worsened or patients experienced unacceptable side effects. A large proportion (57%) had nonsquamous lung cancer (NSCLC), and approximately one third (32%) had previously received immunotherapy. The main aim was to measure the effect on overall survival.

Overall Survival Results

The study compared patients receiving tumor-treating fields therapy (the treatment group) with those receiving standard treatment alone (the control group).

All Patients:

• In the treatment (TTF) group, median follow-up was 10.6 months, ranging from less than 6.1 months for some patients to as long as 33.7 months for others.
• In the control group, median follow-up was 9.5 months, ranging from less than 0.1 months for some patients to as long as 32.1 months for others.

In terms of overall survival, meaning how long patients remained alive:

• In the TTF group, median overall survival was 13.2 months (with the most reliable estimates ranging from 10.3 to 15.5 months).
• In the control group, median overall survival was 9.9 months (with the most reliable estimates ranging from 8.1 to 11.5 months).

These findings show that patients in the treatment group lived longer than those in the control group (hazard ratio 0.74, indicating a statistically significant difference, P = 0.035).

After One Year:

• In the treatment group, 53% of patients were still alive (with the most reliable estimate ranging from 44% to 61%).
• In the control group, 42% of patients were still alive (with the most reliable estimate ranging from 33% to 50%).

Patients Receiving Immunotherapy:

• Treatment Group: Median overall survival was 18.5 months (ranging from less than 10.6 months for some patients to as long as 30.3 months for others). After one year, 60% of patients were still alive.
• Control Group: Median overall survival was 10.8 months (ranging from less than 8.2 months for some patients to as long as 18.4 months for others). After one year, 46% of patients were still alive.

Patients Receiving Docetaxel:

• Treatment Group: Median overall survival was 11.1 months (ranging from less than 8.2 months for some patients to as long as 14.1 months for others). After one year, 46% of patients were still alive.
• Control Group: Median overall survival was 8.7 months (ranging from less than 6.3 months for some patients to as long as 11.3 months for others). After one year, 38% of patients were still alive.

These findings show that patients receiving immunotherapy lived longer with tumor-treating fields therapy (a statistically significant difference, P = 0.030). Among patients receiving docetaxel, however, the difference was not statistically significant (P = 0.28).

Patients With Nonsquamous NSCLC:

• Treatment Group: Mean survival was 12.6 months (ranging from less than 8.8 months for some patients to as long as 19.8 months for others).
• Control Group: Mean survival was 9.9 months (ranging from less than 6.9 months for some patients to as long as 16.4 months for others).
• The difference between the treatment and control groups in this subgroup was not statistically significant (P = 0.28).

Patients With Squamous NSCLC:

• Treatment Group: Mean survival was 13.9 months (ranging from less than 9.7 months for some patients to as long as 17.1 months for others).
• Control Group: Mean survival was 10.1 months (ranging from less than 8.3 months for some patients to as long as 14.3 months for others).
• The difference between treatment and control in this subgroup was borderline statistically significant (P = 0.050).

Approximately one third of patients (28%) also received further treatment after disease progression. The most commonly used drugs were docetaxel (31%) and gemcitabine (27%).

Side Effects

• Treatment Group: Severe side effects (grade 3 or higher) occurred in 59% of patients.
• Control Group: Severe side effects occurred in 56% of patients.
• The most common side effects were: leukopenia (14%), pneumonia (10%) and anemia (8%).

Serious Side Effects:

• Serious side effects occurred in 53% of patients in the treatment group and 38% in the control group.

Treatment Discontinuation:

• Treatment was discontinued because of side effects in 36% of the treatment group and 20% of the control group.
• Tumor-treating fields therapy was discontinued because of side effects in 14% of patients.

Side Effects Related to Tumor-Treating Fields:

• Side effects related to tumor-treating fields were reported in 71% of patients.
• 85% of these side effects were mild or moderate (grade 1 or 2) skin and subcutaneous tissue disorders.
• No deaths related to tumor-treating fields therapy were reported.

Conclusion

TTF therapy stands out as a promising treatment for people with lung cancer. Particularly in patients who have received platinum-based treatment, it can significantly extend overall survival compared with standard therapies without increasing side effects. An even greater survival extension was observed in patients receiving immunotherapy. These encouraging results suggest that TTF therapy could be an effective treatment option for metastatic NSCLC and could receive FDA approval.