TY - JOUR
T1 - Treatment recommendations to cancer patients in the context of FDA guidance for next generation sequencing
AU - Dy, Grace K.
AU - Nesline, Mary K.
AU - Papanicolau-Sengos, Antonios
AU - Depietro, Paul
AU - Levea, Charles M.
AU - Early, Amy
AU - Chen, Hongbin
AU - Grand'Maison, Anne
AU - Boland, Patrick
AU - Ernstoff, Marc S.
AU - Edge, Stephen
AU - Akers, Stacey
AU - Opyrchal, Mateusz
AU - Chatta, Gurkamal
AU - Odunsi, Kunle
AU - Pabla, Sarabjot
AU - Conroy, Jeffrey M.
AU - Glenn, Sean T.
AU - Defedericis, Hanchun T.
AU - Burgher, Blake
AU - Andreas, Jonathan
AU - Giamo, Vincent
AU - Qin, Maochun
AU - Wang, Yirong
AU - Kanehira, Kazunori
AU - Lenzo, Felicia L.
AU - Frederick, Peter
AU - Lele, Shashikant
AU - Galluzzi, Lorenzo
AU - Kuvshinoff, Boris
AU - Morrison, Carl
N1 - Publisher Copyright:
© 2019 The Author(s).
PY - 2019/1/18
Y1 - 2019/1/18
N2 - 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.
AB - 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.
KW - Comprehensive genomic profiling
KW - FDA guidance
KW - Next generation sequencing
KW - Physician treatment recommendations
UR - http://www.scopus.com/inward/record.url?scp=85060136041&partnerID=8YFLogxK
U2 - 10.1186/s12911-019-0743-x
DO - 10.1186/s12911-019-0743-x
M3 - Article
C2 - 30658646
AN - SCOPUS:85060136041
SN - 1472-6947
VL - 19
JO - Bmc Medical Informatics and Decision Making
JF - Bmc Medical Informatics and Decision Making
IS - 1
M1 - 14
ER -