First-line treatment options for epidermal growth factor receptor (EGFR) sensitising mutation-positive advanced Non- Small Cell Lung Cancer (NSCLC)

A substantially higher proportion of mutations in the EGFR tyrosine kinase is observed in Asian populations. Tumours that possess mutations in EGFR are highly sensitive to TKIs. Randomised phase III studies on various TKIs gefitinib10-14, erlotinib15, 16and afatinib5, 17versus chemotherapy exist. EGFR-TKI treatment resulted in significantly increased overall response rates (ORR) (HR 2.08 95% CI 1.75 2.46 p 0.0001) 18and in a meta-analysis of data from trials examining the role of EGFR-TKI in all major clinical settings, EGFR-TKI treatment was associatedwith a lower risk of disease progression in the first line (HR 0.43 95% CI 0.38 0.49 p 0.001) and subsequent line setting (HR 0.34 95% CI 0.2 0.6 p 0.001). 19To date, no phase III trial has demonstrated overall survival (OS) benefit with EGFR-TKI use.19This is likely confounded by treatment post progression in both comparator arms.

Cost Effectiveness

The cost effectiveness of EGFR targeted therapy has been addressed in several papers.20-22Of particular note, in a local analysis of the cost effectiveness of EGFR testing followed by first line gefitinib and second line chemotherapy in EGFR mutants versus the practice of no EGFR testing (e.g. by clinical phenotype alone), first line chemotherapy followed by second line gefitinib, it was demonstrated that the major driver of cost savings was not providing gefitinib to patients who are not likely to benefit supporting the implementation of EGFR mutation testing prior to initiation of first line systemic therapy.21The calculated incremental cost and quality-adjusted life year (QALY) were USD $15,197 and 0.27 with an incremental cost effective ratio (ICER) of USD $56,916 per QALY.21

Recommendations on First Line Treatment Options for EGFR Sensitizing Mutation Positive Advanced NSCLC

The workgroup committee unanimously recommends adopting NCCN guidelines.

1. Either of the EGFR-TKIs gefitinib, erlotinib or afatinib should be considered in the treatment of advanced NSCLC harboring EGFR sensitizing mutations (category 1).

2. Should the mutation be discovered in the midst of first line treatment, the systemic therapy can be interrupted or first line chemotherapy can be completed prior to starting EGFR-TKI (category 2A).