DURHAM, NC — To help guide therapeutic decisions for patients with advanced stage non-small cell lung cancer, Next-Generation Sequencing (NGS) gene panels are often completed.

A presentation at the recent 2020 American Society of Clinical Oncology meeting, which was presented virtually, noted that patients with highly-actionable gene variants might benefit from improved therapeutic treatments and reduced toxicities with use of targeted agents.1

Duke University/ Durham VA Health Care System-led researchers emphasized that, “Ensuring appropriate prescription of targeted therapies is therefore of high importance.”

The study team sought to identify barriers to targeted agent use within the VHA National Precision Oncology Program. To that end, a retrospective evaluation examined the cohort of NSCLC patients who underwent NGS multigene panels through NPOP between July 2015 and February 2019.

Researchers assigned a level of evidence for drug actionability to each observed oncogenic gene variant using an artificial intelligence offering; IBM Watson for Genomics: WfG). WfG Level 1 and 2A evidence was reviewed by NPOP staff to exclude gene variants that did not conform to NPOP Level 1 and 2A definitions.

The study team obtained anti-neoplastic drug prescriptions and oncology provider for all included patients from the VHA Corporate Data Warehouse. The members also reviewed clinical notes of patients who did not receive targeted agents to categorize the reasons.

Results indicated that, of 1764 NSCLC patients who successfully underwent NGS gene panel testing, 156 (8.9%) received therapeutic level 1 (7.3%) or 2A (1.6%) options for targeted agents based on WfG evidence analysis. In total, 117 (6.6%) patients had NPOP Level 1 and 2A gene variants, all within ALK, BRAF, EGFR, ERBB2, MET and RET. Of these, 49 (41.2%) patients were not prescribed available targeted agents.

Researchers said the three most common reasons were:

  • Treating provider did not comment on NGS results (30.7%),

  • Patient did not carry a diagnosis of advanced stage disease (18.4%), and

  • Patient had begun an alternative systemic therapy prior to completion of sequencing (16.3%).

The study advised that no patient was denied access to a Level 1 or 2A targeted drug due to utilization-management review.

“A substantial minority of patients with advanced NSCLC bearing highly-actionable gene variants are not prescribed available targeted agents,” the authors concluded. “Further provider- and pathologist-directed educational effort are needed, as well as implementation of health informatics systems to provide near real-time decision support for test ordering and interpretation.”

  1. Vashistha V, Armstrong J, Winski D, Price M, et. Al. (2020, May 29-31.) Barriers to prescribing targeted therapies for NSCLC patients with highly actionable gene variants in the VA National Precision Oncology Program. ASCO20 Virtual Scientific Program. https://meetinglibrary.asco.org/record/185999/abstract