Treatment recommendations to cancer patients in the context of FDA guidance for next generation sequencing

Grace K. Dy, Mary K. Nesline, Antonios Papanicolau-Sengos, Paul Depietro, Charles M. Levea, Amy Early, Hongbin Chen, Anne Grand'Maison, Patrick Boland, Marc S. Ernstoff, Stephen Edge, Stacey Akers, Mateusz Opyrchal, Gurkamal Chatta, Kunle Odunsi, Sarabjot Pabla, Jeffrey M. Conroy, Sean T. Glenn, Hanchun T. Defedericis, Blake BurgherJonathan Andreas, Vincent Giamo, Maochun Qin, Yirong Wang, Kazunori Kanehira, Felicia L. Lenzo, Peter Frederick, Shashikant Lele, Lorenzo Galluzzi, Boris Kuvshinoff, Carl Morrison

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Background: Regulatory approval of next generation sequencing (NGS) by the FDA is advancing the use of genomic-based precision medicine for the therapeutic management of cancer as standard care. Recent FDA guidance for the classification of genomic variants based on clinical evidence to aid clinicians in understanding the actionability of identified variants provided by comprehensive NGS panels has also been set forth. In this retrospective analysis, we interpreted and applied the FDA variant classification guidance to comprehensive NGS testing performed for advanced cancer patients and assessed oncologist agreement with NGS test treatment recommendations. Methods: NGS comprehensive genomic profiling was performed in a CLIA certified lab (657 completed tests for 646 patients treated at Roswell Park Comprehensive Cancer Center) between June 2016 and June 2017. Physician treatment recommendations made within 120 days post-test were gathered from tested patients' medical records and classified as targeted therapy, precision medicine clinical trial, immunotherapy, hormonal therapy, chemotherapy/radiation, surgery, transplant, or non-therapeutic (hospice, surveillance, or palliative care). Agreement between NGS test report targeted therapy recommendations based on the FDA variant classification and physician targeted therapy treatment recommendations were evaluated. Results: Excluding variants contraindicating targeted therapy (i.e., KRAS or NRAS mutations), at least one variant with FDA level 1 companion diagnostic supporting evidence as the most actionable was identified in 14% of tests, with physicians most frequently recommending targeted therapy (48%) for patients with these results. This stands in contrast to physicians recommending targeted therapy based on test results with FDA level 2 (practice guideline) or FDA level 3 (clinical trial or off label) evidence as the most actionable result (11 and 4%, respectively). Conclusions: We found an appropriate "dose-response" relationship between the strength of clinical evidence supporting biomarker-directed targeted therapy based on application of FDA guidance for NGS test variant classification, and subsequent treatment recommendations made by treating physicians. In view of recent changes at FDA, it is paramount to define regulatory grounds and medical policy coverage for NGS testing based on this guidance.

Original languageEnglish
Article number14
JournalBMC Medical Informatics and Decision Making
Issue number1
StatePublished - Jan 18 2019


  • Comprehensive genomic profiling
  • FDA guidance
  • Next generation sequencing
  • Physician treatment recommendations


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