EGFR Mutation Testing of non-squamous NSCLC: Impact and Uptake during Implementation of Testing Guidelines in a Population-Based Registry Cohort from Northern New Zealand

Mark McKeage, Mark Elwood, Sandar Tin Tin, Prashannata Khwaounjoo, Phyu Aye, Angie Li, Karen Sheath, Phillip Shepherd, George Laking, Nicola Kingston, Christopher Lewis, Donald Love

Since 2013, clinical practice guidelines recommend EGFR mutation testing of non-squamous NSCLC to select advanced-stage patients for first-line treatment using EGFR-TKIs. We aimed to determine population-based trends in the real-world uptake and impact in routine practice of these recently updated testing guidelines. A population-based observational study was conducted of notifications to the New Zealand Cancer Registry of patients eligible for EGFR testing diagnosed in northern New Zealand between January 2010 and April 2014. The main study variable was EGFR mutation testing. Main outcome measures (overall survival and dispensing of EGFR-TKIs) were extracted from prospectively archived electronic databases until October 2015. The population-based cohort of 1857 patients had an average age of 70 years. Most had adenocarcinoma and metastatic disease at diagnosis. EGFR testing was undertaken in 500 patients (27%) with mutations detected in 109 patients (22%). EGFR testing increased during the period of study from <5% to 67% of patients (P < 0.0001). Full uptake of testing by all eligible patients was limited by a lack of availability of specimens for testing and variable testing referral practices. The proportion of patients treated with EGFR-TKIs decreased during the same time period, both among untested patients (from 12.2% to 2.8% (P < 0.0001)) and in the population as a whole (from 13.7% to 10.6% (P < 0.05)). EGFR testing was associated with prolonged overall survival (Adjusted HR = 0.76 (95% CI, 0.65-0.89) Log-rank P < 0.0001) due at least in part to the much longer overall survival achieved by mutation-positive patients, of whom 79% received EGFR-TKIs. Compared to untested EGFR-TKI-treated patients, mutation-positive EGFR-TKI-treated patients received EGFR-TKIs for longer, and survived longer both from the start of EGFR-TKI treatment and date of their diagnosis. In this real world setting, high uptake of EGFR testing was achieved and associated with major changes in EGFR-TKI prescribing and improved health outcomes. Modifiable factors determined testing uptake. Study registration ACTRN12615000998549.