PMID- 30921175
OWN - NLM
STAT- MEDLINE
DCOM- 20190408
LR  - 20210109
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 98
IP  - 13
DP  - 2019 Mar
TI  - Combination strategies based on epidermal growth factor receptor (EGFR) tyrosine 
      kinase inhibitors for cancer patients: Pooled analysis and subgroup analysis of 
      efficacy and safety.
PG  - e14135
LID - 10.1097/MD.0000000000014135 [doi]
LID - e14135
AB  - BACKGROUND: Combination therapy based on epidermal growth factor receptor (EGFR) 
      tyrosine kinase inhibitors (TKIs) is an emerging trend in cancer treatment, but 
      the clinical value of EGFR-TKIs combination therapy remains controversial. Thus, 
      we conducted a comprehensive analysis of randomized controlled trials (RCTs) 
      comparing EGFR-TKIs combination therapies with monotherapies, aiming to evaluate 
      the safety and efficacy of EGFR-TKIs based combination therapy and to find a more 
      beneficial combination strategy. METHODS: We searched for clinical studies that 
      evaluated EGFR-TKIs combination therapy in cancer. We extracted data from these 
      studies to evaluate the relative risk (RR) of overall response rate (ORR) and 
      grade 3/4 treatment-related adverse events (AEs), the hazard ratios (HRs) of 
      overall survival (OS), and progression-free survival (PFS). RESULTS: Fourteen 
      RCTs were identified (n = 3774). Treatments included combinations of EGFR-TKIs 
      and chemotherapy, combinations of EGFR-TKIs and radiotherapy, and combinations of 
      EGFR-TKIs and bevacizumab. EGFR-TKIs combination therapies showed higher ORR [RR: 
      1.62; 95% confidence interval (95% CI):1.16-2.26; P = .005], PFS (HR: 0.76; 95% 
      CI: 0.64-0.89; P = .001), and OS (HR: 0.88; 95% CI: 0.79-0.97; P = .013) values 
      than monotherapies. However, higher grade 3/4 treatment-related AEs (RR: 1.79; 
      95% CI: 1.02-3.15; P = .000) were observed in combination therapy than in 
      monotherapy. CONCLUSION: Our pooled analysis and subgroup analysis results showed 
      that the addition of chemotherapy to EGFR-TKIs better benefits PFS and safety. 
      Adding bevacizumab was associated with better ORR and OS. The efficacy and safety 
      of a bevacizumab-EGFR-TKIs-chemotherapy combination should be investigated 
      further.
FAU - Xu, Ran
AU  - Xu R
AD  - Medical School of Nantong University.
FAU - Shao, Hong
AU  - Shao H
AD  - Nanjing Normal University.
FAU - Zhu, Jing
AU  - Zhu J
AD  - The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, 
      Jiangsu.
FAU - Ju, Qianqian
AU  - Ju Q
AD  - Department of Thoracic Surgery, Affiliated Hospital of Nantong University, 
      Nantong, China.
FAU - Shi, Hui
AU  - Shi H
AD  - Department of Thoracic Surgery, Affiliated Hospital of Nantong University, 
      Nantong, China.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Antineoplastic Agents, Immunological/administration & dosage/pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & 
      dosage/pharmacology
MH  - Bevacizumab/administration & dosage/*pharmacology
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy/mortality/pathology/radiotherapy
MH  - Colorectal Neoplasms/drug therapy/mortality/pathology/radiotherapy
MH  - Disease-Free Survival
MH  - Drug Therapy/methods
MH  - ErbB Receptors/*antagonists & inhibitors
MH  - Erlotinib Hydrochloride/administration & dosage/pharmacology
MH  - Gefitinib/administration & dosage/pharmacology
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/mortality/pathology/radiotherapy
MH  - Protein Kinase Inhibitors/administration & dosage/adverse effects/*pharmacology
MH  - Radiotherapy/methods
MH  - Randomized Controlled Trials as Topic
PMC - PMC6456063
COIS- The authors report no conflicts of interest.
EDAT- 2019/03/29 06:00
MHDA- 2019/04/09 06:00
PMCR- 2019/03/15
CRDT- 2019/03/29 06:00
PHST- 2019/03/29 06:00 [entrez]
PHST- 2019/03/29 06:00 [pubmed]
PHST- 2019/04/09 06:00 [medline]
PHST- 2019/03/15 00:00 [pmc-release]
AID - 00005792-201903290-00001 [pii]
AID - MD-D-18-05251 [pii]
AID - 10.1097/MD.0000000000014135 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2019 Mar;98(13):e14135. doi: 10.1097/MD.0000000000014135.