@article{3034424,
    title = "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: the European Thoracic
Oncology Platform (ETOP 10-16) BOOSTER trial",
    author = "Sooy, R. A. and Han, J. -Y. and Dafni, U. and Cho, B. C. and Yeo, C. M. and and Nadal, E. and Carcereny, E. and de Castro, J. and Sala, M. A. and and Bernabe, R. and Coate, L. and Provencio Pulla, M. and Campelo, R. Garcia and and Cuffe, S. and Hashemi, S. M. S. and Fruh, M. and Massuti, B. and and Garcia-Sanchez, J. and Domine, M. and Majem, M. and Sanchez-Torres, J. and -M. and Britschgi, C. and Pless, M. and Dimopoulou, G. and and Roschitzki-Voser, H. and Ruepp, B. and Rosell, R. and Stahel, R. A. and and Peters, S. and ETOP 10-16 BOOSTER Collaborators",
    journal = "Annals of Oncology",
    year = "2022",
    volume = "33",
    number = "2",
    pages = "181-192",
    publisher = "Elsevier",
    issn = "0923-7534, 1569-8041",
    doi = "10.1016/j.annonc.2021.11.010",
    keywords = "EGFR mutations; NSCLC; osimertinib; bevacizumab; randomised controlled
trial",
    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."
}