Barriers to Targeted Therapies for NSCLC Patients with Highly Actionable Gene Variants in the Veterans Health Affairs Program

Therapeutic decisions for patients with advanced stage non–small-cell lung cancer (NSCLC) are often guided by next-generation sequencing (NGS) gene panels. The use of targeted agents in patients identified with highly actionable gene variants may lead to improved therapeutic treatments and reduced toxicities. In this study, investigators sought to identify barriers to the use of targeted agents within the Veterans Health Affairs, (VHA) National Precision Oncology Program (NPOP).

A retrospective evaluation examined the cohort of patients with NSCLC who underwent NGS multigene panels through the NPOP between July 2015 and February 2019. Using the artificial intelligence tool IBM Watson for Genomics (WfG), a level of evidence for drug actionability was assigned to each observed oncogenic gene variant. Level 1 and 2A evidence from the WfG tool was reviewed by NPOP staff to exclude gene variants that did not conform to NPOP level 1 and 2A definitions. Antineoplastic drug prescriptions and oncology provider notes were obtained from the VHA Corporate Data Warehouse for all included patients. Clinical notes of patients who did not receive targeted agents were reviewed, and the reasons for not receiving those prescriptions were categorized.

Of 1764 patients with NSCLC 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. A total of 117 (6.6%) patients had NPOP level 1 and 2A gene variants, all within ALK, BRAF, EGFR, ERBB2, MET, and RET. Of these patients, 49 (41.2%) were not prescribed available targeted agents.

The 3 most common reasons that patients did not receive available target agents were identified. In 32.4% of cases, patients did not have metastatic disease. In 24.3%, the treating provider did not comment on NGS results. Finally, in 19.0% of cases, the provider did not feel that the patient was a candidate for targeted therapy due to toxicities or the patient’s performance status.

Among those who did not receive targeted management, there was no mention of NGS results in the clinical notes of 51.4% of patients. In 5.4% of patients not receiving targeted management, providers felt that a chemotherapy-based regimen was urgently required while the results of NGS were still pending. No patients were denied access to a level 1 or 2A targeted drug due to utilization-management review.

A substantial number of patients with advanced NSCLC who were identified with highly actionable gene variants were not prescribed available targeted agents in this cohort of patients within the VHA NPOP. The investigators conclude that further provider- and pathologist-directed educational efforts are necessary. In addition, they advise that implementation of health informatics systems to provide near real-time decision support for test ordering and interpretation is needed.

Source: 2020 ASCO Annual Meeting. Abstract 2005.