Rolof G P Gijtenbeek1, Vincent van der Noort2, Joachim G J V Aerts3, Jeske A Staal-van den Brekel4, Egbert F Smit5, Frans H Krouwels6, Frank A Wilschut7, T Jeroen N Hiltermann8, Wim Timens9, Ed Schuuring9, Joost D J Janssen10, Martijn Goosens11, Paul M van den Berg12, A Joop de Langen13, Jos A Stigt14, Ben E E M van den Borne15, Harry J M Groen8, Wouter H van Geffen1, Anthonie J van der Wekken8. 1. Dept of Respiratory Medicine, Medical Centre Leeuwarden, Leeuwarden, The Netherlands. 2. Dept of Biometrics, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands. 3. Dept of Pulmonary Diseases, Erasmus University Medical Centre, Rotterdam, The Netherlands. 4. Dept of Respiratory Medicine, Hospital Group Twente, Almelo/Hengelo, The Netherlands. 5. Dept of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands. 6. Dept of Respiratory Medicine, Spaarne Hospital, Hoofddorp, The Netherlands. 7. Dept of Respiratory Medicine, Gelderse Vallei Hospital, Ede, The Netherlands. 8. Dept of Pulmonary Diseases, University of Groningen and University Medical Centre Groningen, Groningen, The Netherlands. 9. Dept of Pathology and Medical Biology, University of Groningen and University Medical Centre Groningen, Groningen, The Netherlands. 10. Dept of Respiratory Medicine, Máxima Medical Centre, Eindhoven/Veldhoven, The Netherlands. 11. Dept of Pulmonary Medicine, Gelre Hospitals, Zutphen, The Netherlands. 12. Dept of Respiratory Medicine, Maasstad Hospital, Rotterdam, The Netherlands. 13. Dept of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 14. Dept of Respiratory Medicine, Isala Hospital, Zwolle, The Netherlands. 15. Dept of Pulmonary Diseases, Catharina Hospital, Eindhoven, The Netherlands.
Abstract
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 13.7 months (95% CI 5.2-18.8) for CPE and 10.3 months (95% CI 7.1-15.5; hazard ratio (HR) 0.62, 95% CI 0.25-1.57) for erlotinib monotherapy; when compensating for number of days receiving erlotinib, PFS of the CPE arm was superior (HR 0.24, 95% CI 0.07-0.83; p=0.02). ORR was 64% for CPE versus 55% for erlotinib monotherapy. Median overall survival was 31.7 months (95% CI 21.8-61.9 months) for CPE compared to 17.2 months (95% CI 11.5-45.5 months) for erlotinib monotherapy (HR 0.58, 95% CI 0.22-1.41 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.
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 13.7 months (95% CI 5.2-18.8) for CPE and 10.3 months (95% CI 7.1-15.5; hazard ratio (HR) 0.62, 95% CI 0.25-1.57) for erlotinib monotherapy; when compensating for number of days receiving erlotinib, PFS of the CPE arm was superior (HR 0.24, 95% CI 0.07-0.83; p=0.02). ORR was 64% for CPE versus 55% for erlotinib monotherapy. Median overall survival was 31.7 months (95% CI 21.8-61.9 months) for CPE compared to 17.2 months (95% CI 11.5-45.5 months) for erlotinib monotherapy (HR 0.58, 95% CI 0.22-1.41 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.
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