R A Soo1, J-Y Han2, U Dafni3, B C Cho4, C M Yeo5, E Nadal6, E Carcereny7, J de Castro8, M A Sala9, R Bernabé10, L Coate11, M Provencio Pulla12, R Garcia Campelo13, S Cuffe14, S M S Hashemi15, M Früh16, B Massuti17, J Garcia-Sanchez18, M Dómine19, M Majem20, J-M Sanchez-Torres21, C Britschgi22, M Pless23, G Dimopoulou24, H Roschitzki-Voser25, B Ruepp25, R Rosell26, R A Stahel27, S Peters28. 1. Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore. 2. National Cancer Center, Center for Lung Cancer, Goyang, Republic of Korea. 3. National and Kapodistrian University of Athens, Athens, Greece; Frontier Science Foundation Hellas, Athens, Greece. 4. Yonsei Cancer Center, Yonsei University College of Medicine, Division of Medical Oncology, Seoul, Republic of Korea. 5. Medical Oncology Department, Tan Tock Seng Hospital, Singapore, Singapore. 6. Medical Oncology Department, ICO L'Hospitalet, Barcelona, Spain. 7. Medical Oncology Department, Institut Català d'Oncologia Badalona Hospital Germans Trias i Pujol, B-ARGO Group, Badalona, Spain. 8. Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain. 9. Medical Oncology Department, Hospital Universitario Basurto, Bilbao, Spain. 10. Medical Oncology Department, Hospital Virgen del Rocio, Sevilla, Spain. 11. Mid-Western Cancer Centre and University Hospital Limerick, Limerick, Ireland. 12. Hospital Puerta de Hierro, Majadahonda Medical Oncology Service, Madrid, Spain. 13. Medical Oncology Department, Hospital Teresa Herrera, La Coruña, Spain. 14. Department of Medical Oncology, St. James's Hospital, Dublin, Ireland. 15. Department of Pulmonary Diseases, Amsterdam UMC, VU University Medical Center, Amsterdam, Netherlands. 16. Cantonal Hospital St. Gallen, Oncology and Hematology, St. Gallen, Switzerland; Department of Oncology, Inselspital Bern, Bern, Switzerland. 17. Medical Oncology Department, Hospital General Universitario Alicante, Alicante, Spain. 18. Medical Oncology Service, Hospital Arnau Vilanova, Valencia, Spain. 19. Department of Oncology, Hospital Universitario Fundacion Jimenez Díaz (IIS-FJD), Madrid, Spain. 20. Medical Oncology Department, Hospital De La Santa Creu I Sant Pau, Barcelona, Spain. 21. Medical Oncology Department, Hospital Universitario de la Princesa, Madrid, Spain. 22. Department of Medical Oncology and Hematology, University Hospital Zurich, Comprehensive Cancer Center Zurich, Zurich, Switzerland. 23. Cantonal Hospital Winterthur, Oncology and Haematology, Winterthur, Switzerland. 24. Frontier Science Foundation Hellas, Athens, Greece. 25. European Thoracic Oncology Platform (ETOP), Coordinating Office, Bern, Switzerland. 26. Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona, Spain; Catalan Institute of Oncology (ICO), Honorary Consultant, Barcelona, Spain. 27. European Thoracic Oncology Platform (ETOP), Coordinating Office, Bern, Switzerland. Electronic address: Rolf.Stahel@etop-eu.org. 28. Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland.
Abstract
BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.
BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.
Authors: U Dafni; R A Soo; S Peters; Z Tsourti; P Zygoura; K Vervita; J-Y Han; J De Castro; L Coate; M Früh; S M S Hashemi; E Nadal; E Carcereny; M A Sala; R Bernabé; M Provencio; S Cuffe; H Roschitzki-Voser; B Ruepp; R Rosell; R A Stahel Journal: ESMO Open Date: 2022-06-10