Clinical Utility of Rapid Genotyping in Advanced Lung Cancer.

PURPOSE

Targeted therapy is the cornerstone of treatment of advanced -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 mutations and reduce time to initiation (TTI) of epidermal growth factor receptor (EGFR)-directed therapy.

PATIENTS AND METHODS

We performed rapid testing for L858R mutations and exon 19 deletions on paraffin-embedded or frozen section biopsy specimens from newly diagnosed patients with metastatic NSCLC by using an -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 tests and identified mutations in 43 patients (18%). With NGS results as a reference, sensitivity and specificity of the rapid 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 ( < .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 37 days; = .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.