Author: Lei Deng, MD Roswell Park Comprehensive Cancer Center   Live report from ASCO23, Chicago, IL June 6, 2023   LBA9005 Tumor Treating Field (TTFields) therapy with standard of care (SOC) in metastatic non-small cell lung cancer (mNSCLC) following platinum failure: Randomized, phase 3 LUNAR study.   Key points:

• In phase 3 LUNAR trial, NSCLC patients were enrolled following progression on or after platinum-based treatment
• The trial included two arms: TTFields + ICI/docetaxel vs. ICI/docetaxel
• Improved OS was reported: 13.2 vs. 9.9 (HR 0.74, 95% CI 0.56-0.98).
• TTFields combination (HR 0.63) with ICI associated with more OS benefit than docetaxel (HR 0.81)
• TTFields appear to have synergistic effects with ICI

  Tumor Treating Field (TTField) is a novel anti-cancer approach by alternating electrical fields that disrupt the mitotic division of cancer cells. It has been approved by US FDA for glioblastoma and mesothelioma1-3. In this phase 3 LUNAR trial, non-small cell lung cancer (NSCLC) patients were enrolled, following progression on or after platinum-based treatment. Patients in the comparator arm received immune check point inhibitor (ICI) or docetaxel, while those in the experimental arm received additional TTFields. The primary endpoint was OS.   In 2023 ASCO annual meeting, the LUNAR study was presented in Chicago4. 31% of patients received prior ICI. OS was significantly improved (13.2 vs. 9.9 months, HR 0.74, 95% CI 0.56-0.98). Median PFS was 4.8 vs. 4.1 months (HR 0.85, 95% CI 0.67-1.11). Of note, 31 % of patients received prior immune checkpoint inhibitors. Interestingly, patients receiving ICI combination with TTFields appeared to have benefited more. Among patients with ICI + TTFields, the OS was 18.5 vs. 10.8 months (HR 0.63, 95% CI 0.41-0.96); among patients with docetaxel + TTFields, the OS was 11.1 vs. 8.7 months (HR 0.81, 95% CI 0.55-1.19). TTFields had similar adverse effects to control group.   The subgroup analysis suggested a synergistic effect of TTFields with ICI. It would be interesting to watch the outcome of TTFields combination with first line ICI based treatment.  

1. Stupp R, Taillibert S, Kanner A, et al. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA 2017;318:2306-2316.
2. Stupp R, Taillibert S, Kanner AA, et al. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA 2015;314:2535-2543.
3. Ceresoli GL, Aerts JG, Dziadziuszko R, et al. Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial. Lancet Oncol 2019;20:1702-1709.
4. Leal et al. Tumor Treating Field (TTFields) therapy with standard of care (SOC) in metastatic non-small cell lung cancer (mNSCLC) following platinum failure: Randomized, phase 3 LUNAR study. Presented at 2023 ASCO, Chicago, June 2-6, 2023.