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||Broad Genomic Profiling in Patients with Advanced Lung Cancer: Empirically Assessing Adoption, Clinical Utility, and the Value of Additional Evidence in an Evolving Landscape of Cancer Care
Personalized cancer treatment is becoming a reality. The real-world adoption of broad genomic profiling (BGP)
has enabled the simultaneous testing of hundreds of potentially targetable genetic alterations in patients with
cancer. Professional societies have endorsed BGP in clinical practice for several cancer types, including
advanced stage non-small cell lung cancer (aNSCLC). Yet evidence regarding the impact of BGP on patient
outcomes is constantly evolving, with changes in the availability, utilization, and efficacy of targeted agents. As
such, BGP use raises a fundamental question in cancer care: how can stakeholders make the most informed
decisions in the presence of uncertainty? We posit that Value of Information (VOI) analysis, which explicitly
quantifies the trade-off between the benefits of collecting further evidence compared to a decision based on
current evidence, can be used to guide decisions regarding BGP. In this proposal, we address the critical need
to understand real-world 1) BGP use and its impact on 2) clinical decision-making, 3) treatment outcomes and
costs and 4) the value of additional research to empirically inform decisions about the adoption of BGP into
cancer care by leveraging the strengths of multiple complementary, real-world datasets.
Aim 1: Utilization of BGP across contemporary U.S. cancer care. We will examine BGP use in advanced
cancer and drivers of testing within patients with (Aim 1A) Medicare 100% Fee-for-Service and Medicare
Advantage and (Aim 1B) Blue Cross Blue Shield insurance coverage.
Aim 2: BGP results and their impact on treatment patterns in NSCLC. We will quantify the frequency of
actionable mutations among patients with aNSCLC (Aim 2A) and assess the relationship between BGP and
cancer management strategy, given that less than half of patients with a targetable mutation may receive the
corresponding FDA-approved targeted therapy (Aim 2B).
Aim 3: BGP cost and survival. We will determine the relationship between BGP use and cancer care costs
(Aim 3A) and overall and cancer-specific survival (Aim 3B).
Aim 4: Cost Effectiveness & Value of Information. We will use VOI analysis to determine whether additional
evidence/research is needed to support the use of BGP. Specifically, we will compare the long-term health and
cost outcomes associated with 1st line BGP in patients with aNSCLC (currently recommended but
controversial) with two alternate strategies that focus on a smaller number of genetic tests. We will quantify
critical gaps in the evidence that drive uncertainty regarding effectiveness of BGP and quantify the value of
conducting additional research on BGP in order to improve decisions about optimal implementation of BGP.
The proposed research is significant given uncertainty regarding the use and effectiveness of BGP, innovative
given the triangulation across multiple large datasets and incorporation of VOI to guide practice and inform
policy, and clinically relevant given the high burden of advanced cancer and the burgeoning use of BGP.