Clinical Utility of Rapid EGFR Genotyping in Advanced Lung Cancer

Ibiayi Dagogo-Jack; Christopher G. Azzolli; Florian Fintelmann; Mari Mino-Kenudson; Anna F. Farago; Justin F. Gainor; Ginger Jiang; Zofia Piotrowska; Rebecca S. Heist; Inga T. Lennes; Jennifer S. Temel; Meghan J. Mooradian; Jessica J. Lin; Subba R. Digumarthy; Julie M. Batten; Hayley Robinson; Vania Nose; Miguel Rivera; Valentina Nardi; Dora Dias-Santagata; Long P. Le; Lecia V. Sequist; Martha Pitman; Jo-Anne O. Shepard; Alice T. Shaw; A. John Iafrate; Jochen K. Lennerz

Disclosures

JCO Precis Oncol. 2018;2018(2) 

In This Article

Abstract and Introduction

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.

Conclusion: Rapid genotyping facilitates earlier initiation of EGFR-directed therapies without compromising NGS workflows.

Introduction

Non–small-cell lung cancer (NSCLC) is a heterogeneous disease composed of unique molecular subsets with distinct clinical outcomes.[1,2] Multiple randomized studies have established the superiority of molecularly targeted therapies versus chemotherapy for the treatment of EGFR-mutant and ALK-positive NSCLC.[3–6] In other molecular subsets, single-arm studies confirm that treatment with targeted therapies can induce durable responses.[7,8] As drugs that target these molecular drivers are approved for first-line treatment, genotyping in newly diagnosed NSCLC is considered the standard of care.[9]

Because of the need to interrogate a growing number of genes, next-generation sequencing (NGS) has largely replaced traditional single-gene assays.[10] Guidelines endorsed by oncology and pathology societies recommend that molecular testing turnaround times not exceed 10 working days.[9] Genotyping by NGS requires complex bioinformatics that can create treatment delays. Some patients with NSCLC present with symptomatic disease that requires initiation of treatment before molecular testing results are available.[11] To our knowledge, the impact of molecular testing turnaround time on clinical decision making has not been formally assessed in NSCLC.

Here, we evaluated whether the addition of an epidermal growth factor receptor (EGFR)–specific assay to NGS at diagnosis produced accurate results and reduced time to initiation (TTI) of EGFR-directed therapy. We selected EGFR-mutant NSCLC on the basis of its relatively high prevalence (10% to 15%) among patients with NSCLC,[12] the lack of overlap between EGFR mutations and other clinically relevant molecular alterations,[13] and the fact that EGFR inhibitors were readily available for hospitalized patients. We hypothesized that concurrent rapid genotyping would improve clinical care without compromising comprehensive NGS-based genotyping efforts.

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