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607 TTFields therapy with an immune checkpoint inhibitor in metastatic non-small cell lung cancer (mNSCLC) with progression on/after platinum-based therapy: histology subgroups in the pivotal LUNAR study
  1. Jeffrey Ward1,
  2. Ticiana A Leal2,
  3. Rupesh Kotecha3,
  4. Rodryg Ramlau4,
  5. Li Zhang5,
  6. Janusz Milanowski6,
  7. Manuel Cobo Dols7,
  8. Jaromír Roubec8,
  9. Luboš Petruželka9,
  10. Libor Havel10,
  11. Sujith Kalmadi11,
  12. Zoran Andric12,
  13. Thierry Berghmans13,
  14. David E Gerber14,
  15. Goetz Kloecker15,
  16. Rajiv Panikkar16,
  17. Joachim Aerts17,
  18. Angelo Delmonte18,
  19. Miklos Pless19,
  20. Richard Greil20,21,
  21. Christian Rolfo22,
  22. Wallace Akerley23,
  23. Michael Eaton24,
  24. Mussawar Iqbal25 and
  25. Corey Langer26
  1. 1Washington University School of Medicine, St Louis, MO, USA
  2. 2Emory University School of Medicine, Atlanta, GA, USA
  3. 3Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA
  4. 4Poznan University of Medical Sciences, Poznan, Poland
  5. 5Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
  6. 6Medical University of Lublin, Lublin, Poland
  7. 7Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, Spain
  8. 8Nemocnice AGEL Ostrava-Vítkovice, Ostrava, Czech Republic
  9. 9General University Hospital in Prague, Prague, Czech Republic
  10. 10Thomayer Hospital, Prague, Czech Republic
  11. 11Ironwood Cancer and Research Centers, Chandler, AZ, USA
  12. 12Clinical Hospital Centre Bezanijska Kosa, Belgrade, Serbia
  13. 13Jules Bordet Institute, Hôpitaux Universitaires de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium
  14. 14Harold C. Simmons Comprehensive Cancer Center, UT Texas Southwestern Medical Center, Dallas, TX, USA
  15. 15University of Louisville, Louisville, KY, USA
  16. 16Geisinger Cancer Institute, Danville, PA, USA
  17. 17The Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdamn, Netherlands
  18. 18IRCCS Istituto Romagnolo per lo Studio dei Tumori ‘Dino Amadori’ (IRST), Meldola, Italy
  19. 19Kantonsspital Winterthur, Winterthur, Switzerland
  20. 20Salzburg Cancer Research Institute-Center for Clinical Cancer and Immunology Trials (SCRI-CCCIT); Paracelsus Medical University, Salzburg, Austria
  21. 21Cancer Cluster, Salzburg, Austria
  22. 22Center for Thoracic Oncology, Tisch Cancer Institute at Icahn School of Medicine, New York, NY, USA
  23. 23Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
  24. 24St Francis Hospital, Indianapolis, IL, USA
  25. 25College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
  26. 26Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Tumor Treating Fields (TTFields) are electric fields that disrupt cancer cell survival, leading to immunogenic cell death and enhanced antitumor immune responses. TTFields therapy delivered by a noninvasive portable device is FDA-approved for glioblastoma and mesothelioma. The global pivotal LUNAR study (NCT02973789) demonstrated improved overall survival (OS) for TTFields combined with investigator’s choice immune checkpoint inhibitor (ICI) or docetaxel (standard of care [SOC] at time of study design) vs SOC alone in patients with mNSCLC progressing on/after platinum-based therapy (HR 0.74; P=0.035).

Methods Adults with mNSCLC progressing on/after platinum therapy were randomized 1:1 to TTFields+ICI/docetaxel or ICI/docetaxel alone. TTFields (150 kHz) were delivered continuously until progression or intolerable toxicity. An exploratory analysis examined OS by histology and safety in the ICI subgroup.

Results Of 276 randomized patients, 134 (49%) assigned to receive an ICI had median age 65 years (range 23–86); 66% were male. 94% had received only one prior line of therapy. PD-L1 tumor proportion score (TPS; available for 76 patients) showed PD-L1-positive tumors (TPS ≥1%) were balanced between non-squamous and squamous subgroups (30/50 [60%] and 18/26 [69%]). TTFields+ICI vs ICI was also balanced for histology: non-squamous (37/66 [56%] vs 37/68 [54%]) and squamous (29/66 [44%] vs 31/68 [46%]). Median OS (mOS) was 18.5 months (mo) for TTFields+ICI vs 10.8 mo for ICI alone (HR 0.63 [95% CI 0.41–0.96]; P=0.03). mOS (95% CI) for TTFields+ICI vs ICI alone in patients with non-squamous disease was 19.7 (8.8–31.1) mo vs 9.9 (5.6–22.2) mo; HR 0.63 (95% CI 0.36–1.12) P=0.11, and for squamous was 15.4 (9.6–35.4) mo vs 12.9 (9.6–19.3) mo; HR 0.69 (95% CI 0.37–1.30) P=0.25. Adverse event (AE) rates (all-cause) were comparable between TTFields+ICI (99%) and ICI alone (91%) groups, including pneumonitis (5% vs 6%) and other immune-related AEs. TTFields-related AEs occurred in 73% of ICI-treated patients; most were grade 1/2 local skin irritation; 5% reported a grade 3 AE. No grade 4 AEs or deaths were attributed to TTFields.

Conclusions Analysis of OS benefit in patients receiving TTFields with an ICI for mNSCLC after progression on or after platinum therapy did not detect a difference between squamous and non-squamous disease. OS benefit occurred without exacerbating the toxicity of ICI therapy.

Acknowledgements Medical writing support under the direction of the authors was provided by Chelsea Higgins, CMPP (Global Publications, Novocure Inc, US), and Rose Goodchild and Melissa Purves, CMPP (Prime, UK), funded by Novocure Inc.

Trial Registration; NCT02973789

Ethics Approval All patients provided written informed consent. The study protocol and all amendments were approved by the relevant ethics committee and competent authority at each participating site. This study conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was conducted in compliance with good clinical practice guidelines (EN ISO 14155:2011) and all relevant national/regional regulations.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

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