Tumor Treating Fields vs Standard Therapy in Treatment-Resistant Metastatic NSCLC

1. The median OS was 13.2 months with TTFields arm vs 9.9 months with standard arm, with an HR of 0.74. This effect was more pronounced in treatment with immune checkpoint inhibitors.

2. Most frequent TTFields therapy-related adverse events were grade 1 to 2 skin related events

Evidence Rating Level: 1 (Excellent)

Study Rundown: Metastatic non-small-cell lung cancer (NSCLC) remains difficult to treat once there is progression on platinum-based therapy. Tumor Treating Fields (TTFields) therapy, which disrupts mitosis using electric fields, has shown promise in other cancers (glioblastoma and pleural mesothelioma) with little adverse effects. This study aimed to evaluate the addition of TTFields therapy to standard systemic therapy (docetaxel or immune checkpoint inhibitor) vs standard systemic therapy alone in patients with metastatic NSCLC who progressed with platinum-based therapy. The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), overall response rate (ORR), quality-of-life (QoL), and adverse events. The median OS was 13.2 months with TTFields arm vs 9.9 months with standard arm, with an HR of 0.74. Subgroup analysis shows that within immune checkpoint inhibitors, the median OS was 18.5 months vs 10.8 months respectively with an HR of 0.63, whereas within patients treated with docetaxel, the median OS was 11.1 months vs 8.7 months respectively, with an HR of 0.81. Median PFS was 4.8 months vs 4.1 months respectively with an HR 0.85. The ORR was 20.4% in the TTFields arm vs 17.3% in the standard arm. With regards to safety, grade 3 or higher adverse events were reported 59% of patients in the TTFields arm vs 56% of patients in the standard arm. The most frequent TTFields therapy-related adverse events were grade 1 to 2 events and included dermatitis (39%), pruritus (12%), rash (9%), and skin ulcer (8%). QoL was similar in both arms throughout the study. The strengths of this study included its high quality methodology and the limitations of this study included the size of the study as well as the funding source of the investigators/statisticians. Overall, this study showed some benefit to adding TTFields therapy to standard systemic therapies in patients with metastatic NSCLC who have progressed after platinum-based therapy, without increasing systemic toxicities.

Click to read the study in the Lancet

Relevant Reading: A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer

In-Depth [randomized controlled trial]: This phase 3, open-label study randomized adults with metastatic NSCLC who progressed (with radiological evidence) after platinum-based systemic therapy into two treatment arm, TTFields therapy to the thorax with standard therapy (137 patients) or standard therapy alone (139 patients). Standard systemic therapy was chosen based on investigator’s best clinical judgement prior to randomization, either an immune checkpoint inhibitor (nivolumab, pembrolizumab, or atezolizumab) or docetaxel. Median follow-up was 10.6 months for the TTFields arm and 9.5 months for standard arm. The median length of time for each TTFields therapy sessions were 56-57% of each day. Median OS was 13.2 months (95%CI, 10.3-15.5) with TTFields arm vs 9.9 months (95%CI, 8.1-11.5) with standard arm, with an HR of 0.74 (95%CI. 0.56-0.98, p=0.035). Subgroup analysis shows that within immune checkpoint inhibitors, the median OS was 18.5 months (95%CI, 10.6-30.3) vs 10.8 months (95%CI, 8.2-18.4) respectively with an HR of 0.63 (95%CI, 0.41-0.96, p=0.030), whereas within patients treated with docetaxel, the median OS was 11.1 months (95%CI, 8.2-14.1) vs 8.7 months (95%CI, 6.3-11.3) respectively, with an HR of 0.81 (95%CI, 0.55-1.19, p=0.28). Median PFS was 4.8 months (95%CI, 4.1-5.7) vs 4.1 months (95%CI, 3.1-4.6) respectively with an HR 0.85 (95%CI, 0.67-1.11, p=0.23). The ORR was 20.4% (95%CI, 14.0-28.2) in the TTFields arm vs 17.3% (95%CI, 11.4-24.6) in the standard arm. With regards to safety, grade 3 or higher adverse events were reported 59% of patients in the TTFields arm vs 56% of patients in the standard arm. The most frequent TTFields therapy-related adverse events were grade 1 to 2 events and included dermatitis (39%), pruritus (12%), rash (9%), and skin ulcer (8%). QoL was similar in both arms throughout the study. Overall, this study showed some benefit to adding TTFields therapy to standard systemic therapies in patients with metastatic NSCLC who have progressed after platinum-based therapy, without increasing systemic toxicities.

Image: PD

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