Opinion: Tumor-Treating Fields Hold Promise in Metastatic Non–Small Cell Lung Cancer

Amanda Brink, DNP, APRN, FNP-BC, AOCNP

Tumor-treating fields (TTFields) therapy is an emerging area of oncological treatment for various solid tumors.

TTFields consist of electrical fields transmitted transdermally to tumors through a portable medical device worn by patients.1 This device contains electrodes, which are placed over the body in locations predominantly affected by cancer—the locations are tailed to the type of cancer that an individual has.¹ TTFields have the capacity to disrupt intracellular processes crucial for cancer cell survival and growth.² Currently, the FDA has approved TTFields for the treatment of glioblastoma² and unresectable pleural mesothelioma,³ however, multiple other clinical trials are underway to explore the application of TTFields across other solid tumors.

LUNAR Study

According to findings from the pivotal open-label, phase 3 LUNAR study (NCT02973789) that were published in The Lancet Oncology, patients with metastatic non-small-cell lung cancer (NSCLC) who had previously progressed on platinum-based systemic therapy experienced significantly improved overall survival after receiving TTFields therapy alongside standard treatment compared to patients who received standard therapy alone.²

Eligible participants were adults with metastatic NSCLC whose disease had progressed on platinum-based systemic therapy.

In the study, patients were treated with standard systemic therapy, which consisted of an immune checkpoint inhibitor (ICI) such as nivolumab (Opdivo), pembrolizumab (Keytruda), or atezolizumab (Tecentriq), or docetaxel. The choice of treatment was based on the treating investigator’s best clinical judgment and standard practice guidelines. The choice of systemic therapy was made before the randomization to TTFrields or standard of care.

Patients were then randomly assigned to receive TTFields to the thorax along with standard therapy or to receive standard therapy alone. TTFields therapy, which has been shown to have maximal anticancer effects at 150 kHz, was delivered continuously to the thoracic region of the patient’s body. The recommended duration of device usage is 75% of the day, or 18 hours per day. Patients continued with treatment until either their disease progressed or unacceptable toxicity occurred.

Median overall survival (OS) was significantly longer in patients treated with TTFields therapy and standard therapy (n=137), at 13.2 months (95% CI, 10.3-15.5), compared to standard therapy alone (n=139), at 9.9 months (95% CI, 8.1-11.5 [HR, 0.74; 95% CI, 0.56-0.98; P = .035]). The OS rate at 1 year was 53% (95% CI, 44%-61%) for patients treated with TTFields therapy and standard therapy, compared to 42% (95% CI, 33-50) for standard therapy alone.

Patients were divided into subgroups based on the type of standard therapy they received. The median OS for those who received TTFields plus ICI therapy was 18.5 months (95% CI, 10.6-30.3), compared to 10.8 months (95% CI, 8.2-18.4) when treated with ICI alone (HR, 0.63; 95% CI, 0.41-0.96; P = .030). Median OS in patients treated with TTFields and docetaxel was 11.1 months (95% CI, 8.2-14.1), compared with 8.7 months (95% CI, 6.3-11.3) when treated with docetaxel alone (HR, 0.81; 95% CI, 0.55-1.19; P = .028).

Furthermore, the overall response rate in patients treated with TTFields therapy in combination with standard therapy was 20.4% (95% CI, 14.0%-28.2%) versus 17.3% (95% CI, 11.4%-24.6%) for standard therapy alone. Five patients achieved a complete response. Four of these 5 patients were treated with TTFields and ICI therapy and 1 was treated with ICI therapy alone.

Regarding device usage, patients treated with ICI therapy wore their TTFields therapy devices for a median of 56% of the day for the first 3 months. Patients treated with docetaxel wore their devices for a median of 57% of the day. The recommended amount of time to wear the device is at least 75% of the day and this was achieved by 19% of the patients treated with ICI therapy and 26% of patients treated with docetaxel.

Nursing Considerations

An important nursing consideration when interpreting this data and assessing its potential impact on patients is the tolerance of wearing the TTFields device.

TTFields therapy has not been shown to be associated with systemic toxicity. In this study, 12% of patients who received combined treatment with TTFields and standard therapy required a dose reduction of their systemic treatment, compared to 14% of patients treated with standard therapy alone. Further, 11% of all enrolled patients discontinued standard therapy due to toxicities related to the standard therapy. Of the patients treated with TTFields, 14% discontinued treatment due to toxicity related to device usage.

The most common adverse event associated with TTFields were grade 1 or 2 skin adverse events including dermatitis in 39% of patients, pruritis in 12% of patients, rash in 9% of patients, and skin ulcer in 8% of patients. TTFields therapy was not shown to be associated with an increased risk of adverse events, including pneumonitis or cardiac toxicity, which could be a concern due to placement of electrodes on the thorax. Patient quality of life, measured by the European Organisation For Research And Treatment Of Cancer Quality-of-Life (EORTC QLQ-30) questionnaire, was similar between both groups.

Oncology nurses provide a great deal of patient education to patients and their caregivers before and during treatment. Nurses may be able to help prevent skin toxicity in patients being treated with TTFields therapy by educating patients and caregivers on the prophylactic use of topical steroids or calcineurin inhibitor creams.

In conclusion, this study showed that TTFields therapy, when given in addition to standard systemic therapy, improves OS in patients with metastatic NSCLC over standard-of-care systemic therapy alone, without increasing the risk of systemic toxicities. In my opinion, this treatment modality is a promising new way to treat this patient population.

References

1. Moser JC, Salvador E, Deniz K, et al. The mechanisms of action of Tumor Treating Fields. Cancer res. 2022;82(20): 3650-3658. doi:10.1158/0008-5472.CAN-22-0887
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. doi:10.1016/S1470-2045(23)00344-3
3. Kutuk T, Appel H, Avendano MC, et al. Feasibility of tumor treating fields with pemetrexed and platinum-based chemotherapy for unresectable malignant pleural mesothelioma: Single-center, real-world data. Cancers (Basel). 2022;14(8):2020. doi:10.3390/cancers14082020