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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 ORR. (A) Forest plots of OR and 95% CI; (B) Results of sensitivity analysis; and (C) Begg’s funnel plot analysis of publication bias. OR, odds ratio; ORR, objective response rate; s.e., standard error.
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f2: Meta-analysis of the predictive value of K-ras mutation for ORR. (A) Forest plots of OR and 95% CI; (B) Results of sensitivity analysis; and (C) Begg’s funnel plot analysis of publication bias. OR, odds ratio; ORR, objective response rate; s.e., standard error.

Mentions: The impact of K-ras mutation on the ORR of NSCLC patients treated with EGFR-TKI therapy was evaluated based on 29 studies (Table 2). K-ras mutation was associated with reduced objective response in NSCLC patients with a pooled OR of 0.22 (95% CI, 0.13-0.35) (Figure 2A). Fixed-effect model was used because heterogeneity across the trials was not significant (I2=0%; P=0.999). The sensitivity analysis indicated that no individual study changed the pooled OR significantly (Figure 2B), suggesting that the result was reliable. Publication bias was significant in Begg’s test (P=0.049), but not in Egger’s test (P=0.090) (Figure 2C). Patients included in two studies39,54 apparently originated from the same center. Given that the independence of the two studies could not be confirmed, another analysis excluding the prior one of the aforementioned studies was conducted considering the possibility of duplicate patient population. The pooled OR was 0.22 (95% CI, 0.13-0.35) in a fixed effect model (I2=0%; P=0.998), with publication bias reduced significantly (P values in Egger’s and Begg’s tests were 0.101 and 0.072, respectively).


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 ORR. (A) Forest plots of OR and 95% CI; (B) Results of sensitivity analysis; and (C) Begg’s funnel plot analysis of publication bias. OR, odds ratio; ORR, objective response rate; s.e., standard error.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Meta-analysis of the predictive value of K-ras mutation for ORR. (A) Forest plots of OR and 95% CI; (B) Results of sensitivity analysis; and (C) Begg’s funnel plot analysis of publication bias. OR, odds ratio; ORR, objective response rate; s.e., standard error.
Mentions: The impact of K-ras mutation on the ORR of NSCLC patients treated with EGFR-TKI therapy was evaluated based on 29 studies (Table 2). K-ras mutation was associated with reduced objective response in NSCLC patients with a pooled OR of 0.22 (95% CI, 0.13-0.35) (Figure 2A). Fixed-effect model was used because heterogeneity across the trials was not significant (I2=0%; P=0.999). The sensitivity analysis indicated that no individual study changed the pooled OR significantly (Figure 2B), suggesting that the result was reliable. Publication bias was significant in Begg’s test (P=0.049), but not in Egger’s test (P=0.090) (Figure 2C). Patients included in two studies39,54 apparently originated from the same center. Given that the independence of the two studies could not be confirmed, another analysis excluding the prior one of the aforementioned studies was conducted considering the possibility of duplicate patient population. The pooled OR was 0.22 (95% CI, 0.13-0.35) in a fixed effect model (I2=0%; P=0.998), with publication bias reduced significantly (P values in Egger’s and Begg’s tests were 0.101 and 0.072, respectively).

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