Abstract 375: Oncologist use and perception of large panel next generation tumor sequencing
Authors: Schram Alison M. , Reales Dalicia , Galle Jesse , Cambria Roy , Durany Robert , Feldman Darren , Sherman Eric , Rosenberg Jonathan , D'Andrea Gabriella , Baxi Shrujal , Janjigian Yelena , Tap William , Dickler Maura , Baselga José , Taylor Barry , Chakravarty Debyani , Gao Jianjiong , Schultz Nikolaus D. , Solit David B. , Berger Michael F. , Hyman David M. 
Published: July 2017

At Memorial Sloan Kettering, we have used a clinically validated custom hybridization capture-based NGS assay (MSK-IMPACT) to sequence the tumors of more than 10,000 patients. We sought to determine physician perception and use of these results, including whether they changed management and the reasoning behind this decision-making. All physicians who ordered MSK-IMPACT testing for patients where it was not considered routine were asked to complete a questionnaire quarterly (Table). Physician determination of genomic “actionability” was compared to OncoKB, a curated knowledge base of somatic variants (OncoKB.org).

Responses were received from 146 of 258 physicians emailed (57%) regarding 1932 of 9147 patients (21%). Physician respondents comprised a diversity of cancer specialties including medical oncology (67%), pediatric oncology (8%), surgery (6%), radiation oncology (5%), and neuro-oncology (5%). A total of 49 cancer types were represented. Physicians indicated that sequencing altered management in 331 (20%) of profiled patients in need of a treatment change. Among those in whom treatment was reportedly not altered, physicians indicated the presence of at least one actionable alteration in 55% (805/1474) of cases. However, only 45% of these cases harbored a genomic variant annotated as actionable by OncoKB. Among patients in whom physicians deemed the report non-actionable, 12% had OncoKB annotated actionable variants. Across the cases annotated as potentially actionable by OncoKB, physicians identified an actionable alteration in 81% of cases. At the time of data analysis, 297 (15%) patients had been enrolled in at least one clinical trial of targeted therapy at MSKCC including 224 (12%) patients on genomically-matched trials, 76% of whom participated after IMPACT profiling. As the clinical adoption of NGS panels expands, continued education of physicians as well as maintained knowledge bases for annotation will be necessary to expand the utility of this approach and the opportunity for precision medicine.

QuestionsResponses, N (%)DID alter treatment, as follows:1. Patient enrolled to a therapeutic protocol at MSKCC265 (14)2. Patient enrolled to a therapeutic protocol at another institution15 (1)3. Patient treated with off-label use of an FDA approved therapy43 (2)DID NOT alter treatment, as follows:4. Actionable mutation(s) identified, but no therapeutic protocol was available175 (9)5. Actionable mutation(s) identified, but patient declined participation in, or was ineligible for, available therapeutic protocol115 (6)6. Actionable mutation(s) identified, but patient deteriorated, progressed, or died before results could be used176 (9)7. Actionable mutation(s) identified and therapeutic study available, but patient has not recurred/progressed since MSK-IMPACT result339 (18)8. No actionable mutation identified669 (35)Other135 (7)TOTAL1932

Citation Format: Alison M. Schram, Dalicia Reales, Jesse Galle, Roy Cambria, Robert Durany, Darren Feldman, Eric Sherman, Jonathan Rosenberg, Gabriella D'Andrea, Shrujal Baxi, Yelena Janjigian, William Tap, Maura Dickler, José Baselga, Barry Taylor, Debyani Chakravarty, Jianjiong Gao, Nikolaus D. Schultz, David B. Solit, Michael F. Berger, David M. Hyman. Oncologist use and perception of large panel next generation tumor sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 375. doi:10.1158/1538-7445.AM2017-375