1. A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations
- Author
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R.A. Soo, J.-Y. Han, U. Dafni, B.C. Cho, C.M. Yeo, E. Nadal, E. Carcereny, J. de Castro, M.A. Sala, R. Bernabé, L. Coate, M. Provencio Pulla, R. Garcia Campelo, S. Cuffe, S.M.S. Hashemi, M. Früh, B. Massuti, J. Garcia-Sanchez, M. Dómine, M. Majem, J.-M. Sanchez-Torres, C. Britschgi, M. Pless, G. Dimopoulou, H. Roschitzki-Voser, B. Ruepp, R. Rosell, R.A. Stahel, S. Peters, Rolf Stahel, Solange Peters, Ross Soo, Ji-Youn Han, Martin Früh, Mariano Provencio, Linda Coate, Urania Dafni, Anita Hiltbrunner, Barbara Ruepp, Heidi Roschitzki-Voser, Adriana Gasca-Ruchti, Nino Giacomelli, Rosita Kammler, Nesa Marti, Lionel Nobs, Mariana Pardo-Contreras, Rita Pfister, Anne-Christine Piguet, Sabrina Ribeli-Hofmann, Virginia Rodriguez Martinez, Susanne Roux, Magdalena Sanchez-Hohl, Mirjam Schneider, Robin Schweri, Sandra Troesch, Isabel Zigomo, Zoi Tsourti, Panagiota Zygoura, Marie Kassapian, Katerina Vervita, Georgia Dimopoulou, Charitini Andriakopoulou, Maria Fernandez, Eva Pereira, Carolina Simona, Lisa Tucker, Jillian Burnes, Aisling Barrett, Meghan McGrillen, Catherine Berset, Christine Biaggi, Martin Reist, Priska Rentsch, Sinead Cuffe, Sayed Hashemi, Ernest Nadal, Enric Carcereny, Javier de Castro, Maria Angeles Sala, Bernabé Reyes, Mariano Provencio Pulla, Rosario Garcia Campelo, Bartomeu Massutí, Jose Garcia, Manuel Dómine, Margarita Majem, Jose Miguel Sanchez, Christian Britschgi, Miklos Pless, Chong Ming Yeo, Byoung Chul Cho, Pulmonary medicine, and CCA - Cancer Treatment and quality of life
- Subjects
Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Bevacizumab ,Population ,Phases of clinical research ,bevacizumab ,NSCLC ,law.invention ,T790M ,Randomized controlled trial ,law ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Humans ,Osimertinib ,education ,Protein Kinase Inhibitors ,education.field_of_study ,Acrylamides ,Aniline Compounds ,business.industry ,Standard treatment ,Hematology ,EGFR mutations ,ErbB Receptors ,osimertinib ,Mutation ,business ,randomised controlled trial ,medicine.drug - 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.
- Published
- 2022