PMID- 35046801
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220121
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Osimertinib Rechallenge With Bevacizumab vs. Chemotherapy Plus Bevacizumab in 
      EGFR-Mutant NSCLC Patients With Osimertinib Resistance.
PG  - 746707
LID - 10.3389/fphar.2021.746707 [doi]
LID - 746707
AB  - At present, treatment options for osimertinib resistance are very limited. Dual 
      inhibition of the vascular endothelial growth factor (VEGF) and epidermal growth 
      factor receptor (EGFR) significantly improved the progression-free survival (PFS) 
      of advanced EGFR-mutant non-small cell lung cancer (NSCLC). After EGFR-tyrosine 
      kinase inhibitor (TKI) resistance, EGFR-TKI continuation combined with VEGF 
      inhibitors still had clinical benefits. It is unclear whether the addition of 
      bevacizumab after osimertinib progresses will prolong the duration of the 
      osimertinib benefit. We screened 1289 patients with NSCLC and finally included 96 
      patients to evaluate osimertinib combined with bevacizumab (osi + bev) versus 
      chemotherapy combined with bevacizumab (che + bev) for patients with acquired 
      resistance to osimertinib. The overall response rate (ORR) for osi + bev and chem 
      + bev was 15.8% (6 of 38) and 20.7% (12 of 58), respectively. The median PFS for 
      osi + bev and che + bev was 7.0 and 4.9 months (HR 0.415 95%CI: 0.252-0.687 p = 
      0.001). The median OS for osi + bev and che + bev was 12.6 and 7.1 months (HR 
      0.430 95%CI: 0.266-0.696 p = 0.001). Multivariate analyses showed that no brain 
      metastases and osi + bev treatment after osimertinib resistance correlated with 
      longer PFS (p = 0.044, p = 0.001), while the median PFS of osimertinib less than 
      6 months (p = 0.021) had a detrimental effect on sequent treatment. Only osi + 
      bev treatment was identified as an independent predictor of OS (p = 0.001). The 
      most common adverse events (AEs) of grade >/=3 were hypertension (13.2%) and 
      diarrhea (10.5%) in the osi + bevacizumab group. Neutropenia (24.1%) and 
      thrombocytopenia (19%) were the most common grade >/=3 AEs in the che + bev group. 
      The overall incidence of serious AEs (grade >/=3) was significantly higher in the 
      chemotherapy plus bevacizumab group. Our study has shown the superiority of osi + 
      bev compared to che + bev after the failure of osimertinib, making it a preferred 
      option for patients with acquired resistance to osimertinib.
CI  - Copyright (c) 2022 Cui, Hu, Cui, Wu, Mao, Ma and Liu.
FAU - Cui, Qingli
AU  - Cui Q
AD  - Department of Integrated Traditional Chinese and Western Medicine, Affiliated 
      Cancer Hospital of Zhengzhou University, Zhengzhou, China.
FAU - Hu, Yanhui
AU  - Hu Y
AD  - Nanjing University of Chinese Medicine, Nanjing, China.
FAU - Cui, Qingan
AU  - Cui Q
AD  - Department of Medical Oncology, Affiliated Zhengzhou Central Hospital of 
      Zhengzhou University, Zhengzhou, China.
FAU - Wu, Daoyuan
AU  - Wu D
AD  - Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Mao, Yuefeng
AU  - Mao Y
AD  - Department of Medical Oncology, Second People's Hospital of Pingdingshan, 
      Pingdingshan, China.
FAU - Ma, Dongyang
AU  - Ma D
AD  - Department of Integrated Traditional Chinese and Western Medicine, Affiliated 
      Cancer Hospital of Zhengzhou University, Zhengzhou, China.
FAU - Liu, Huaimin
AU  - Liu H
AD  - Department of Integrated Traditional Chinese and Western Medicine, Affiliated 
      Cancer Hospital of Zhengzhou University, Zhengzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20220103
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8762231
OTO - NOTNLM
OT  - EGFR
OT  - NSCLC
OT  - bevacizumab
OT  - osimertinib rechallenge
OT  - resistance
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/01/21 06:00
MHDA- 2022/01/21 06:01
PMCR- 2022/01/03
CRDT- 2022/01/20 06:01
PHST- 2021/07/27 00:00 [received]
PHST- 2021/11/30 00:00 [accepted]
PHST- 2022/01/20 06:01 [entrez]
PHST- 2022/01/21 06:00 [pubmed]
PHST- 2022/01/21 06:01 [medline]
PHST- 2022/01/03 00:00 [pmc-release]
AID - 746707 [pii]
AID - 10.3389/fphar.2021.746707 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Jan 3;12:746707. doi: 10.3389/fphar.2021.746707. 
      eCollection 2021.