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 K-ras mutation for PFS. (A) Forest plots of HR and 95% CI; (B) Results of sensitivity analysis; (C) Begg’s funnel plot analysis of publication bias; and (D) Filled funnel plot using trim-and-fill method. ○, indicates observed studies; ◙, indicates missed studies. HR, hazard ratio; s.e., standard error.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Meta-analysis of the predictive value of K-ras mutation for PFS. (A) Forest plots of HR and 95% CI; (B) Results of sensitivity analysis; (C) Begg’s funnel plot analysis of publication bias; and (D) Filled funnel plot using trim-and-fill method. ○, indicates observed studies; ◙, indicates missed studies. HR, hazard ratio; s.e., standard error.

Mentions: Data for assessing the impact on PFS according to K-ras mutation status was available in six studies. K-ras mutant patients had shorter PFS compared with wild-type patients with pooled HR of 1.56 (95% CI, 1.27-1.92) (Figure 3A). Fixed-effect model was used when calculating pooled HR for PFS because heterogeneity across trials was not significant (I2=0%; P=0.748). Sensitivity analysis indicated that this result was robust (Figure 3B). Egger’s test revealed slight publication bias (P=0.046), contrary to Begg’s test (P=0.260) (Figure 3C). Thus, a non-parametric “trim-and-fill” method was utilized to adjust the publication bias (Figure 3D). After the trim-and-fill adjustment, two missing studies were added, and the estimated pooled HR was 1.46, with 95% CI ranging from 1.21 to 1.74.


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 K-ras mutation for PFS. (A) Forest plots of HR and 95% CI; (B) Results of sensitivity analysis; (C) Begg’s funnel plot analysis of publication bias; and (D) Filled funnel plot using trim-and-fill method. ○, indicates observed studies; ◙, indicates missed studies. HR, hazard ratio; s.e., standard error.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Meta-analysis of the predictive value of K-ras mutation for PFS. (A) Forest plots of HR and 95% CI; (B) Results of sensitivity analysis; (C) Begg’s funnel plot analysis of publication bias; and (D) Filled funnel plot using trim-and-fill method. ○, indicates observed studies; ◙, indicates missed studies. HR, hazard ratio; s.e., standard error.
Mentions: Data for assessing the impact on PFS according to K-ras mutation status was available in six studies. K-ras mutant patients had shorter PFS compared with wild-type patients with pooled HR of 1.56 (95% CI, 1.27-1.92) (Figure 3A). Fixed-effect model was used when calculating pooled HR for PFS because heterogeneity across trials was not significant (I2=0%; P=0.748). Sensitivity analysis indicated that this result was robust (Figure 3B). Egger’s test revealed slight publication bias (P=0.046), contrary to Begg’s test (P=0.260) (Figure 3C). Thus, a non-parametric “trim-and-fill” method was utilized to adjust the publication bias (Figure 3D). After the trim-and-fill adjustment, two missing studies were added, and the estimated pooled HR was 1.46, with 95% CI ranging from 1.21 to 1.74.

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