Oncologist uptake of comprehensive genomic profile guided targeted therapy.

Mary Nesline ,Felicia L Lenzo,Mateusz Opyrchal,Anne Grand’Maison,Igor Puzanov,Jeffrey M Conroy,Paul Depietro,Kunle Odunsi,Grace K Dy,Sean T Glenn,Shashikant Lele,Marc S Ernstoff,Mark Gardner,Hongbin Chen,Carl Morrison,Stacey N Akers ,Peter J Frederick ,Amy P Early ,Antonios Papanicolau‐Sengos ,Stephen B Edge ,Patrick M Boland ,Gurkamal S Chatta

doi:10.18632/oncotarget.27047

Abstract

We describe the extent to which comprehensive genomic profiling (CGP) results were used by oncologists to guide targeted therapy selection in a cohort of solid tumor patients tested as part of standard care at Roswell Park Comprehensive Cancer Center June 2016–June 2017, with adequate follow up through September 2018 (n = 620). Overall, 28.4% of CGP tests advised physicians about targeted therapy use supported by companion diagnostic or practice guideline evidence. Post-test targeted therapy uptake was highest for patients in active treatment at the time of order (86% versus 76% of treatment naïve patients), but also took longer to initiate (median 50 days versus 7 days for treatment naïve patients), with few patients (2.6%) receiving targeted agents prior to testing. 100% of patients with resistance variants did not receive targeted agents. Treatment naïve patients received immunotherapy as the most common alternative. When targeted therapy given off-label or in a trial was the best CGP option, (7%) of patients received it. Our data illustrate the appropriate and heterogeneous use of CGP by oncologists as a longitudinal treatment decision tool based on patient history and treatment needs, and that some patients may benefit from testing prior to initiation of other standard treatments.

Highlights

Despite growing routine use by oncologists, the usefulness of comprehensive genomic profiling (CGP) by generation sequencing (NGS) for targeted therapy treatment decisions in real world clinical practice has gone largely uncharacterized
Comprehensive genomic profiling (CGP) supports putting these results into practice by leveraging the highthroughput capabilities of generation sequencing (NGS) technologies to simultaneously test for all types of genomic alterations, including mutations, copy number variants and fusions, associated with targeted therapy opportunities for a panel of cancer associated genes
Given that we observed post-test targeted therapy use was most common among patients who were already actively receiving treatment when CGP was ordered, and that few patients were on targeted therapy at the time of test order, we examined how long it took to start targeted therapy

Summary

Introduction

Despite growing routine use by oncologists, the usefulness of comprehensive genomic profiling (CGP) by generation sequencing (NGS) for targeted therapy treatment decisions in real world clinical practice has gone largely uncharacterized. Comprehensive genomic profiling (CGP) supports putting these results into practice by leveraging the highthroughput capabilities of generation sequencing (NGS) technologies to simultaneously test for all types of genomic alterations, including mutations, copy number variants (amplification) and fusions (rearrangements), associated with targeted therapy opportunities for a panel of cancer associated genes. FISH testing for these genes, unlike RNA-based NGS testing, has been shown to be at risk for false positives [4], and may under-report actionable alterations that could result in denying patients treatment with these highly efficacious TKI inhibitors [5, 6]. CGP can detect highly actionable EGFR mutations that predict response to EGFR inhibitors in NSCLC that have been missed by single gene testing [7]

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Conclusion