Date of Award

January 2016

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Maria M. Ciarleglio

Second Advisor

Xinhan Zhao

Abstract

Epidermal growth factor receptor- tyrosine kinase inhibitor (EGFR-TKI) is one of the genetic targeted medicines that is used to treat non-small-cell lung cancer. However, because EGFR-TKIs have a specific target, they are not believed to benefit all non-small-cell cancer patients.

We conducted a meta-analysis synthesizing 9 randomized controlled trials (RCTs) to systematically evaluate the effectiveness of EFGR-TKIs among two patient populations: unselected patients with unknown EGFR mutation status and selected patients harboring EGFR mutation

Among unselected patients, the efficacy of EGFR-TKIs is inferior to chemotherapy. The hazard of disease progression in the EGFR-TKI group is 1.46 times that in the chemotherapy group (95% CI (1.29, 1.65)). This result is consistent in the subgroups of male, smoker, and patients with all subtypes of non-small-cell lung cancer. However, there is no significant difference of hazard of disease progression among subgroups of female and non-smoker.

Among EGFR mutant patients, the efficacy of EGFR-TKIs is superior to chemotherapy. Random effects model estimated the hazard of progression in the EGFR-TKI group to be 0.33 times that in the chemotherapy group (95% CI (0.24, 0.46)). Fixed effect model estimates the hazard of progression in the EGFR-TKIs group to be 0.32 times that in the chemotherapy group (95% CI (0.27, 0.38)).This result is consistent in the subgroups of current smoker, non-smoker, male and female. There is no significant difference of hazard of disease progression among subgroup of past smoker (Pooled HR=0.83 with a 95% CI (0.36,1.92)).

Although EGFR-TKIs have provided an alternate solution for advanced non-small-cell patients, it cannot benefit all patients. Among patients not harboring EGFR mutation, it could be more hazardous than chemotherapy. Among Patients harboring EGFR mutation, it has shown significantly better efficacy than chemotherapy. However, the efficacy of EGFR-TKIs vary considerably among patients who had history of smoking. There is evidence that even among EGFR mutant patients, smoking could hinder the efficacy of EGFR-TKIs. The hazard of disease progression of past smokers is even greater than that of current smokers. More research needs to be done to further explore the pathological relationship between smoking and EGFR-TKI efficacy.

Comments

This is an Open Access Thesis.

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