Clinical Utility of Rapid EGFR Genotyping in Advanced Lung Cancer.

Dagogo-Jack I1, Azzolli CG1, Fintelmann F1, Mino-Kenudson M1, Farago AF1, Gainor JF1, Jiang G1, Piotrowska Z1, Heist RS1, Lennes IT1, Temel JS1, Mooradian MJ1, Lin JJ1, Digumarthy SR1, Batten JM1, Robinson H1, Nose V1, Rivera M1, Nardi V1, Dias-Santagata D1, Le LP1, Sequist LV1, Pitman M1, Shepard JO1, Shaw AT1, Iafrate AJ1, Lennerz JK1.

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Abstract

PURPOSE:

Targeted therapy is the cornerstone of treatment of advanced EGFR-mutant non-small-cell lung cancer (NSCLC). Next-generation sequencing (NGS), the preferred method for genotyping, typically requires several weeks. Here, we assessed workflows designed to rapidly identify patients with actionable EGFR mutations and reduce time to initiation (TTI) of epidermal growth factor receptor (EGFR)-directed therapy.

PATIENTS AND METHODS:

We performed rapid testing for EGFR L858R mutations and exon 19 deletions on paraffin-embedded or frozen section biopsy specimens from newly diagnosed patients with metastatic NSCLC by using an EGFR-specific assay (rapid test). To determine clinical utility, we assessed concordance with NGS results, turnaround time, and TTI of EGFR therapy, and we evaluated reimbursement data.

RESULTS:

Between January 2015 and September 2017, we performed 243 rapid EGFR tests and identified EGFR mutations in 43 patients (18%). With NGS results as a reference, sensitivity and specificity of the rapid EGFR polymerase chain reaction assay were 98% and 100%, respectively. The median turnaround time for NGS was 14 days, compared with 7 days for rapid testing (P < .001). In the rapid group, 95% of patients received an EGFR inhibitor in the first-line setting. The median TTI of EGFR therapy was significantly shorter in the rapid cohort when compared with 121 historical cases (22 v 37 days; P = .01). Escalation of the initiative into an interdisciplinary ultra-rapid next-day frozen-section workflow for highly symptomatic patients (n = 8) resulted in a reduction in the median (± standard deviation) turnaround time to 1 ± 0.4 days and allowed several patients to initiate therapy within 1 week of biopsy. An extended 9-month clinical evaluation phase confirmed operational sustainability (turnaround times: ultra-rapid, 0.81 ± 0.4 days; rapid, 3 ± 1.5 days), and a 63% reimbursement rate indicated financial sustainability.