PMID- 37415629
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230718
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Print)
IS  - 1792-1074 (Linking)
VI  - 26
IP  - 2
DP  - 2023 Aug
TI  - Low‑dose anlotinib combined with EGFR‑TKI can be used as an alternative for 
      EGFR‑TKI‑resistant non‑small cell lung cancer in elderly patients.
PG  - 323
LID - 10.3892/ol.2023.13909 [doi]
LID - 323
AB  - The current treatment options for epidermal growth factor receptor (EGFR) 
      mutation-positive lung cancer in the elderly with tyrosine kinase inhibitor (TKI) 
      resistance are limited. Although chemotherapy combined with vascular endothelial 
      growth factor inhibitors significantly improves progression-free survival (PFS) 
      in TKI-resistant patients, it often cannot be tolerated in elderly patients, 
      leading to treatment failure. Anlotinib is a small molecule inhibitor made in 
      China. The application of low-dose anlotinib in elderly patients with 
      TKI-resistant lung cancer deserves further investigation. A total of 48 elderly 
      patients with non-small cell lung cancer (NSCLC) were enrolled to evaluate the 
      efficacy of anlotinib combined with continuous EGFR-TKI vs. anlotinib monotherapy 
      in patients with acquired EGFR-TKI resistance. Anlotinib was administered at a 
      dose of 6-8 mg per day, lower than the normal dose and known as a low dose, which 
      is well tolerated in elderly patients. There were 25 cases in the combination 
      group and 23 cases in the anlotinib monotherapy group. The primary endpoint of 
      the present study was PFS, and the secondary endpoints were overall survival 
      (OS), response rate and toxicity. The median PFS (mPFS) was significantly longer 
      in the combination group than that in the anlotinib monotherapy group: 6.0 months 
      [95% confidence interval (CI), 4.35-7.65] compared with 4.0 months (95% CI, 
      3.38-4.62) (P=0.002). Analysis of the subgroups showed similar trends in results. 
      The median OS was 32 months (95% CI, 22.04-41.96) in the combination group and 28 
      months (95% CI, 27.13-28.87) in the anlotinib monotherapy group (P=0.217). 
      According to stratification analysis, second-line treatment with anlotinib 
      combined with EGFR-TKI resulted in a better mPFS than third-line treatment (7.5 
      vs. 3.7 months, HR=3.477; 95% CI, 1.117-10.820; P=0.031). In the combination 
      group, patients with gradual/local progression after EGFR-TKI failure had a 
      longer mPFS than those with dramatic progression (7.5 vs. 6.0 months, HR=5.875; 
      95% CI, 1.414-10.460; P=0.015). Multivariate analyses showed that continuous 
      EGFR-TKI combined with anlotinib after EGFR-TKI resistance was associated with 
      longer PFS (P=0.019), whereas dramatic progression (P=0.014) had a detrimental 
      effect on follow-up treatment. Grade 2 adverse events (AEs) were reported in four 
      patients (17.39%) in the anlotinib monotherapy group and eight patients (32.00%) 
      in the combination group. Of these, the most common grade 2 AEs were 
      hypertension, fatigue, diarrhea, paronychia, mucositis and transaminase 
      elevation. There were no grade 3/4/5 AEs. In conclusion, the present study 
      demonstrated that low-dose anlotinib combined with EGFR-TKI is superior to 
      anlotinib alone following EGFR-TKI failure, making it the preferred regimen for 
      elderly patients with acquired EGFR-TKI resistance.
CI  - Copyright: (c) Chen et al.
FAU - Chen, Yi
AU  - Chen Y
AD  - Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 
      Nanjing, Jiangsu 210000, P.R. China.
AD  - Department of Oncology, Nanjing Pukou Central Hospital, Pukou Branch Hospital of 
      Jiangsu Province Hospital, Nanjing, Jiangsu 210000, P.R. China.
FAU - Jiang, Nanyuan
AU  - Jiang N
AD  - Department of Oncology, Nanjing Pukou Central Hospital, Pukou Branch Hospital of 
      Jiangsu Province Hospital, Nanjing, Jiangsu 210000, P.R. China.
FAU - Liang, Xiao
AU  - Liang X
AD  - Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 
      Nanjing, Jiangsu 210000, P.R. China.
FAU - Chen, Nan
AU  - Chen N
AD  - Department of Outpatient, General Hospital of Eastern Theater Command, Nanjing, 
      Jiangsu 210000, P.R. China.
FAU - Chen, Yun
AU  - Chen Y
AD  - Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 
      Nanjing, Jiangsu 210000, P.R. China.
FAU - Zhang, Chen
AU  - Zhang C
AD  - Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 
      Nanjing, Jiangsu 210000, P.R. China.
FAU - Shi, Junfeng
AU  - Shi J
AD  - Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu 210006, P.R. China.
AD  - Department of Molecular and Cellular Biochemistry, Markey Cancer Center, 
      University of Kentucky, Lexington, KY 40506, USA.
FAU - Guo, Renhua
AU  - Guo R
AD  - Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 
      Nanjing, Jiangsu 210000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20230613
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC10320416
OTO - NOTNLM
OT  - anlotinib
OT  - elderly patients
OT  - low dose
OT  - non-small cell lung cancer
OT  - tyrosine kinase inhibitor resistance
COIS- The authors declare that they have no competing interests.
EDAT- 2023/07/07 06:43
MHDA- 2023/07/07 06:44
PMCR- 2023/06/13
CRDT- 2023/07/07 03:54
PHST- 2023/02/02 00:00 [received]
PHST- 2023/05/18 00:00 [accepted]
PHST- 2023/07/07 06:44 [medline]
PHST- 2023/07/07 06:43 [pubmed]
PHST- 2023/07/07 03:54 [entrez]
PHST- 2023/06/13 00:00 [pmc-release]
AID - OL-26-2-13909 [pii]
AID - 10.3892/ol.2023.13909 [doi]
PST - epublish
SO  - Oncol Lett. 2023 Jun 13;26(2):323. doi: 10.3892/ol.2023.13909. eCollection 2023 
      Aug.