iNUDGE: Integration of Liquid Biopsy Based Next Generation Gene Sequencing in Newly Diagnosed NSCLC

Although it remains relatively new, the field of precision medicine—an approach to care that uses an individual’s genetic profile, environment, and lifestyle to help inform treatment decisions—is making major differences for patients around the world. Also known as personalized medicine, this approach can be powerful for people with cancer, where targeted therapies are designed to selectively reach the specific gene driving cancer.

To inform and optimize the effectiveness of these targeted therapies, the National Comprehensive Cancer Network recommends molecular testing for anyone newly diagnosed with metastatic NSCLC. Despite this recommendation, only around half of all NSCLC patients receive this comprehensive genetic testing.

Barriers to molecular testing include insufficient tissue for testing, a lack of infrastructure for obtaining and transporting samples, and extended wait times for results. A project led by researchers at the Penn Center for Cancer Care Innovation (PC3I) at the Abramson Cancer Center sets out to help bring down these barriers with iNUDGE, a provider-team-focused strategy designed to encourage comprehensive genetic testing for patients with metastatic non-squamous NSCLC who had not yet started treatment.

With the goal of implementing Liquid Biopsy-based NGS in Newly Diagnosed NSCLC, the iNUDGE strategy employs electronic health record (EHR) systems to prompt or “nudge” care providers to order plasma-based next-generation gene sequencing (NGS) at initial diagnosis. The “nudge” within each facility’s EHR is designed to increase the ordering of plasma-based NGS at the time of consultation.

Along with testing the effectiveness of the iNUDGE strategy itself, the project aims to understand specific mechanisms affecting the adoption, reach, and effectiveness of the interventions. This includes the ways in which response may differ by race and ethnicity, socioeconomic status, and other key social determinants of health.

Figure 1: EHR-based nudge intervention workflow.

The iNUDGE intervention works by:

• Appearing as an EHR prompt at the time of the first telephone encounter with a new patient coordinator, based on a set of pre-populated molecular questions for all patients with a new diagnosis of NSCLC.

• Allowing determination of whether molecular testing is appropriate for an upcoming new patient prior to the visit.

A behavioral economics (BE) informed nudge strategy was piloted at the Perelman Center for Advanced Medicine (PCAM) with promising results. Through this study, 526 patients with newly diagnosed, stage IV, non-squamous NSCLC received therapy, with 376 in the pre-intervention and 157 in the post-intervention cohort. Across all sites, patients in the post-intervention cohort saw a higher rate of undergoing comprehensive molecular testing (100% versus 88% in the pre-intervention cohort); a higher rate of receiving results of comprehensive molecular testing prior to treatment (90.4% versus 78.2% in the pre-intervention cohort); and a higher rate of guideline concordant care (89.8% versus 78.2% in the pre-intervention cohort).

After iNUDGE demonstrated improvements in comprehensive molecular genotyping for a significantly higher number of patients with NSCLC, an agreement with Loxo@Lilly has extended this work to six additional Penn Medicine sites:

• Lancaster General Hospital
• Penn Medicine Princeton Health
• Penn Medicine Cherry Hill
• Penn Medicine Washington Township
• Penn Presbyterian Medical Center
• Penn Medicine Voorhees

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