%0 Journal Article %A Rolof G.P. Gijtenbeek %A Vincent van der Noort %A Joachim G.J.V. Aerts %A Jeske A. Staal-van den Brekel %A Egbert F. Smit %A Frans H. Krouwels %A Frank A. Wilschut %A T. Jeroen N. Hiltermann %A Wim Timens %A Ed Schuuring %A Joost D.J. Janssen %A Martijn Goosens %A Paul M. van den Berg %A A. Joop de Langen %A Jos A. Stigt %A Ben E.E.M. van den Borne %A Harry J.M. Groen %A Wouter H. van Geffen %A Anthonie J. van der Wekken %T Randomised controlled trial of first-line tyrosine-kinase inhibitor (TKI) versus intercalated TKI with chemotherapy for EGFR-mutated nonsmall cell lung cancer %D 2022 %R 10.1183/23120541.00239-2022 %J ERJ Open Research %P 00239-2022 %V 8 %N 4 %X Introduction Previous studies have shown interference between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and chemotherapy in the cell cycle, thus reducing efficacy. In this randomised controlled trial we investigated whether intercalated erlotinib with chemotherapy was superior compared to erlotinib alone in untreated advanced EGFR-mutated nonsmall cell lung cancer (NSCLC).Materials and methods Treatment-naïve patients with an activating EGFR mutation, ECOG performance score of 0–3 and adequate organ function were randomly assigned 1:1 to either four cycles of cisplatin-pemetrexed with intercalated erlotinib (day 2–16 out of 21 days per cycle) followed by pemetrexed and erlotinib maintenance (CPE) or erlotinib monotherapy. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival, objective response rate (ORR) and toxicity.Results Between April 2014 and September 2016, 22 patients were randomised equally into both arms; the study was stopped due to slow accrual. Median follow-up was 64 months. Median PFS was 8.8 months (95% CI 4.2–18.8) for CPE and 10.3 months (95% CI 7.1–15.5; hazard ratio (HR) 0.78, 95% CI 0.32–1.91) for erlotinib monotherapy; when compensating for number of days receiving erlotinib, PFS of the CPE arm was superior (HR 0.32, 95% CI 0.10–1.01; p=0.02). ORR was 64% for CPE versus 55% for erlotinib monotherapy. Median overall survival was 30.9 months (95% CI 18.5–61.9 months) for CPE compared to 17.2 months (95% CI 11.5–45.5 months) for erlotinib monotherapy (HR 0.66, 95% CI 0.27–1.65 months). Patients treated with CPE had higher rates of treatment-related fatigue, anorexia, weight loss and renal toxicity.Conclusion Intercalating erlotinib with cisplatin-pemetrexed provides a longer PFS compared to erlotinib alone in EGFR-mutated NSCLC at the expense of more toxicity.Intercalated erlotinib with cisplatin-pemetrexed prolongs PFS compared to erlotinib alone (13.7 versus 10.3 months; HR 0.24, 95% CI 0.07–0.83). However, the combination treatment is not favourable due to higher toxicity rates. https://bit.ly/3AIl5bq %U https://openres.ersjournals.com/content/erjor/8/4/00239-2022.full.pdf