TY - JOUR
T1 - 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
T2 - the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial
AU - ETOP 10-16 BOOSTER Collaborators
AU - Soo, R. A.
AU - Han, J. Y.
AU - Dafni, U.
AU - Cho, B. C.
AU - Yeo, C. M.
AU - Nadal, E.
AU - Carcereny, E.
AU - de Castro, J.
AU - Sala, M. A.
AU - Bernabé, R.
AU - Coate, L.
AU - Provencio Pulla, M.
AU - Garcia Campelo, R.
AU - Cuffe, S.
AU - Hashemi, S. M.S.
AU - Früh, M.
AU - Massuti, B.
AU - Garcia-Sanchez, J.
AU - Dómine, M.
AU - Majem, M.
AU - Sanchez-Torres, J. M.
AU - Britschgi, C.
AU - Pless, M.
AU - Dimopoulou, G.
AU - Roschitzki-Voser, H.
AU - Ruepp, B.
AU - Rosell, R.
AU - Stahel, R. A.
AU - Peters, S.
AU - Han, Ji Youn
AU - Früh, Martin
AU - Provencio, Mariano
AU - Coate, Linda
AU - Dafni, Urania
AU - Hiltbrunner, Anita
AU - Ruepp, Barbara
AU - Roschitzki-Voser, Heidi
AU - Gasca-Ruchti, Adriana
AU - Giacomelli, Nino
AU - Kammler, Rosita
AU - Marti, Nesa
AU - Nobs, Lionel
AU - Pardo-Contreras, Mariana
AU - Pfister, Rita
AU - Piguet, Anne Christine
AU - Ribeli-Hofmann, Sabrina
AU - Martinez, Virginia Rodriguez
AU - Roux, Susanne
AU - Sanchez-Hohl, Magdalena
AU - Yeo, Chong Ming
N1 - Publisher Copyright:
© 2021 European Society for Medical Oncology
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - EGFR mutations
KW - NSCLC
KW - bevacizumab
KW - osimertinib
KW - randomised controlled trial
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U2 - 10.1016/j.annonc.2021.11.010
DO - 10.1016/j.annonc.2021.11.010
M3 - Article
C2 - 34839016
AN - SCOPUS:85121658815
SN - 0923-7534
VL - 33
SP - 181
EP - 192
JO - Annals of Oncology
JF - Annals of Oncology
IS - 2
ER -