Limits...
Predictive value of K-ras and PIK3CA in non-small cell lung cancer patients treated with EGFR-TKIs: a systemic review and meta-analysis.

Chen JY, Cheng YN, Han L, Wei F, Yu WW, Zhang XW, Cao S, Yu JP - Cancer Biol Med (2015)

Bottom Line: Odds ratios (ORs) for objective response rate (ORR) and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were calculated.PIK3CA mutation showed similar trends.In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment.

View Article: PubMed Central - PubMed

Affiliation: 1 Department of Immunology, 2 Cancer Molecular Diagnostic Core Laboratory, 3 Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.

ABSTRACT

Objective: A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment of non-small cell lung cancer (NSCLC) patients.

Methods: Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios (ORs) for objective response rate (ORR) and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were calculated.

Results: Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval (CI), 0.13-0.35], shorter PFS (HR =1.56; 95% CI, 1.27-1.92), and shorter OS (HR =1.59; 95% CI, 1.33-1.91) in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA significantly predicted shorter OS (HR =1.83; 95% CI, 1.05-3.20), showed poor ORR (OR =0.70; 95% CI, 0.22-2.18), and shorter PFS (HR =1.79; 95% CI, 0.91-3.53) in NSCLC patients treated with EGFR-TKIs.

Conclusion: K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR-TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment.

No MeSH data available.


Related in: MedlinePlus

Meta-analysis of the predictive value of PIK3CA mutation. (A) Forest plots of OR and 95% CI for ORR; (B) Forest plots of HR and 95% CI for PFS; and (C) Forest plots of HR and 95% CI for OS. OR, odds ratio; HR, hazard ratio.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493374&req=5

f5: Meta-analysis of the predictive value of PIK3CA mutation. (A) Forest plots of OR and 95% CI for ORR; (B) Forest plots of HR and 95% CI for PFS; and (C) Forest plots of HR and 95% CI for OS. OR, odds ratio; HR, hazard ratio.

Mentions: Five studies investigated the predictive role of PIK3CA mutation in NSCLC patients (Table 2). Among these, ORR data were available in four studies, PFS data in two studies, and OS data in three studies. PIK3CA mutant NSCLC patients exhibited similar response to EGFR-TKIs compared with wild-type patients with corresponding pooled OR of 0.70 (95% CI, 0.22-2.18) (Figure 5A). Fixed-effect model was used because heterogeneity across studies was not significant (I2=34.9%; P=0.203). The pooled HR of 1.79 (95% CI, 0.91-3.53) for PFS in a fixed-effect model (I2=0%; P=0.893) suggested that PIK3CA mutant NSCLC patients had similar PFS compared with wild-type patients when treated with EGFR-TKIs (Figure 5B). However, PIK3CA mutation showed a trend toward a significant adverse effect on OS with a pooled HR of 1.83 (95% CI, 1.05-3.20) in NSCLC patients treated with EGFR-TKIs (Figure 5C). Between-study heterogeneity was not significant; thus, the analysis was performed in the fixed-effect model (I2=26.9%; P=0.255).


Predictive value of K-ras and PIK3CA in non-small cell lung cancer patients treated with EGFR-TKIs: a systemic review and meta-analysis.

Chen JY, Cheng YN, Han L, Wei F, Yu WW, Zhang XW, Cao S, Yu JP - Cancer Biol Med (2015)

Meta-analysis of the predictive value of PIK3CA mutation. (A) Forest plots of OR and 95% CI for ORR; (B) Forest plots of HR and 95% CI for PFS; and (C) Forest plots of HR and 95% CI for OS. OR, odds ratio; HR, hazard ratio.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493374&req=5

f5: Meta-analysis of the predictive value of PIK3CA mutation. (A) Forest plots of OR and 95% CI for ORR; (B) Forest plots of HR and 95% CI for PFS; and (C) Forest plots of HR and 95% CI for OS. OR, odds ratio; HR, hazard ratio.
Mentions: Five studies investigated the predictive role of PIK3CA mutation in NSCLC patients (Table 2). Among these, ORR data were available in four studies, PFS data in two studies, and OS data in three studies. PIK3CA mutant NSCLC patients exhibited similar response to EGFR-TKIs compared with wild-type patients with corresponding pooled OR of 0.70 (95% CI, 0.22-2.18) (Figure 5A). Fixed-effect model was used because heterogeneity across studies was not significant (I2=34.9%; P=0.203). The pooled HR of 1.79 (95% CI, 0.91-3.53) for PFS in a fixed-effect model (I2=0%; P=0.893) suggested that PIK3CA mutant NSCLC patients had similar PFS compared with wild-type patients when treated with EGFR-TKIs (Figure 5B). However, PIK3CA mutation showed a trend toward a significant adverse effect on OS with a pooled HR of 1.83 (95% CI, 1.05-3.20) in NSCLC patients treated with EGFR-TKIs (Figure 5C). Between-study heterogeneity was not significant; thus, the analysis was performed in the fixed-effect model (I2=26.9%; P=0.255).

Bottom Line: Odds ratios (ORs) for objective response rate (ORR) and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were calculated.PIK3CA mutation showed similar trends.In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment.

View Article: PubMed Central - PubMed

Affiliation: 1 Department of Immunology, 2 Cancer Molecular Diagnostic Core Laboratory, 3 Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.

ABSTRACT

Objective: A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment of non-small cell lung cancer (NSCLC) patients.

Methods: Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios (ORs) for objective response rate (ORR) and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were calculated.

Results: Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval (CI), 0.13-0.35], shorter PFS (HR =1.56; 95% CI, 1.27-1.92), and shorter OS (HR =1.59; 95% CI, 1.33-1.91) in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA significantly predicted shorter OS (HR =1.83; 95% CI, 1.05-3.20), showed poor ORR (OR =0.70; 95% CI, 0.22-2.18), and shorter PFS (HR =1.79; 95% CI, 0.91-3.53) in NSCLC patients treated with EGFR-TKIs.

Conclusion: K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR-TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment.

No MeSH data available.


Related in: MedlinePlus