Tumour Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell survival, leading to immunogenic cell death and enhanced anti-tumour immune response. In pre-clinical models of non-small cell lung cancer (NSCLC), TTFields amplified the effects of chemotherapy and immune checkpoint inhibitors. This report presents the primary results from a pivotal study of TTFields therapy in metastatic NSCLC.
The LUNAR study is a prospective, randomised controlled phase III trial aimed to test the efficacy and safety of TTFields, using the NovoTTF-200T device, concurrent with standard therapies for stage 4 NSCLC patients, following progression while on or after platinum-based treatment. The device is an experimental, portable, battery-operated device for chronic administration of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumour, by means of surface, insulated electrode arrays.1
METHODS
This randomised, open-label, pivotal phase III study recruited patients at 130 sites in nineteen countries. Participants were aged ≥22 years with metastatic NSCLC progressing on or after platinum-based therapy, with squamous or non-squamous histology and ECOG performance status of ≤2. Previous platinum-based therapy was required, but no restriction was placed on the number or type of previous lines of systemic therapy. Participants were randomly assigned (1:1) to TTFields therapy and standard systemic therapy (investigator’s choice of immune checkpoint inhibitor or docetaxel) or standard therapy alone. Randomisation was performed centrally using variable-blocked randomisation and an interactive voice–web response system, and was stratified by tumour histology, treatment, and region. Systemic therapies were dosed according to local practice guidelines. TTFields therapy (150 kHz) was delivered continuously to the thoracic region with the recommendation to achieve an average of at least 18 h/day device usage. The primary endpoint was overall survival (OS) in the intention-to-treat population. The safety population included all patients who received any study therapy and was analysed according to the treatment received.
FINDINGS
Between 13 February 2017 and 19 November 2021, 276 patients were enrolled and randomly assigned to receive TTFields therapy with standard therapy (n=137) or standard therapy alone (n=139). The median age was 64 years, 178 (64%) were male and 98 (36%) were female, 156 (57%) had non-squamous NSCLC, and 87 (32%) had received a previous immune checkpoint inhibitor. Median follow-up was 10.6 months for patients receiving TTFields therapy with standard therapy, and 9.5 months for patients receiving standard therapy. OS was significantly longer in the TTFields arm than in the standard arm (median 13.2 vs. 9.9 months; HR[95%CI]: 0.74[0.56-0.98], p= 0.035). The one-year OS rate was 53% with TTFields therapy and standard therapy, and 42% with standard therapy alone. In the safety population (n=267), serious adverse events of any cause were reported in 70 (53%) of 133 patients receiving TTFields therapy plus standard therapy and 51 (38%) of 134 patients receiving standard therapy alone. The most frequent grade 3–4 adverse events were leukopenia, pneumonia, and anaemia. TTFields therapy-related adverse events were reported in 95 (71%) of 133 patients, these were mostly grade 1–2 skin and subcutaneous tissue disorders. There were three deaths related to standard therapy and no deaths related to TTFields therapy.
CONCLUSIONS
TTFields therapy added to standard therapy significantly improved OS compared with standard therapy alone in metastatic NSCLC after progression on platinum-based therapy without exacerbating systemic toxicities. These data suggest that TTFields therapy is efficacious in metastatic NSCLC and should be considered as a treatment option in this setting.2
REFERENCES
1. ClinicalTrials.gov ID NCT02973789. LUNAR: Pivotal, Randomized, Open-label Study of Tumour Treating Fields (TTFields) Concurrent With Standard of Care Therapies for Treatment of Stage 4 Non-small Cell Lung Cancer (NSCLC) Following Platinum Failure. https://clinicaltrials.gov/study/NCT02973789?term=NCT02973789&rank=1. Accessed on 27 September 2023.
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