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Background: Radiotherapy (RT) can be used to reduce symptoms and maintain open airways for patients with non-small cell lung cancer when systemic treatment is not sufficient. For some patients, tumor control is not achieved due to radioresistance. Concurrent inhibition of epidermal growth factor receptors has been proposed as a strategy to overcome radioresistance but may increase toxicity. We performed a randomized trial to assess the efficacy, tolerance, and quality of life of concurrent erlotinib and palliative thoracic RT for patients with advanced non-small cell lung cancer., Methods: Patients were randomized 1:1 to RT alone (arm A) or in combination with erlotinib (arm B). A computed tomography (CT) scan at baseline and one at 4-12 weeks after inclusion was used to evaluate treatment response. Adverse events were registered during treatment and the subsequent 30 days. Health-related quality-of-life questionnaires were completed by the patients at baseline, weeks 2, 6, and 20., Results: A total of 114 patients were included. Of the 74 patients with CT scans available for evaluation of treatment effect, there were no significant differences in tumor size reduction between the two groups: median 14.5% reduction in the control arm A and 17.0% in the erlotinib arm B ( p = 0.68). Overall survival was not significantly different between the two treatment arms: 7.0 and 7.8 months in arm A and arm B, respectively (log-rank p = 0.32). There was no significant increase in adverse events in the experimental arm, other than what is expected from erlotinib treatment alone. Overall, patients reported similar quality of life in both treatment arms., Conclusion: Concurrent erlotinib and palliative thoracic RT for patients with advanced non-small cell lung cancer was well tolerated but did not improve the efficacy of the RT., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02714530., Competing Interests: HN has received honoraria from Astra Zeneca. HH has received honoraria for lectures or advisory boards from Astra Zeneca, Janssen, Pfizer and Roche. HE has received honorarium from Sanofi. MB has received honoraria personal/institution from Astra Zeneca, BMS and Pfizer. OB has received honoraria personal and/or institution for lectures or advisory boards from AstraZeneca, Bayer, BMS, BoehringerIngelheim, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Takeda and research grants institution from Amgen, AstraZeneca, GlaxoSmithKline, Pfizer, and Roche/Genentech. BG has received honoraria from Janssen, Pfizer, BMS, AstraZeneca, MSD, Eli Lilly and research support from Astra Zeneca og Roche. VH has received honoraria for talks and advisory boards from Astra Zeneca, Roche, Pierre Fabre, Takeda, BMS, Pfizer and Novartis and has received support for trials from the Norwegian Cancer Society and The regional health authorities in Norway. AH has given talks and advice to pharma companies, all honoraria to the hospital Astra, Roche, Janssen, Novartis, Takeda, Pfizer, BMS, EliLilly, Abbvie, Merck, Sanofi, Bayer, Medicover and received research support from AstraZeneca, Roche, Novartis, Incyte, EliLilly, BMS, Ultimovacs, GSK, the Norwegian Cancer Society, The regional health authorities in Norway, The Norwegian Research Council. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nymoen, Alver, Horndalsveen, Eide, Bjaanæs, Brustugun, Grønberg, Haakensen and Helland.)