journal contribution
posted on 2024-01-12, 08:21 authored by Sarah P. Suehnholz, Moriah H. Nissan, Hongxin Zhang, Ritika Kundra, Subhiksha Nandakumar, Calvin Lu, Stephanie Carrero, Amanda Dhaneshwar, Nicole Fernandez, Benjamin W. Xu, Maria E. Arcila, Ahmet Zehir, Aijazuddin Syed, A. Rose Brannon, Julia E. Rudolph, Eder Paraiso, Paul J. Sabbatini, Ross L. Levine, Ahmet Dogan, Jianjiong Gao, Marc Ladanyi, Alexander Drilon, Michael F. Berger, David B. Solit, Nikolaus Schultz, Debyani Chakravarty For solid tumor samples from the MSK-IMPACT subset of the AACR Project GENIE dataset with n≥100, (a) the median number of oncogenic and actionable (gray), oncogenic and non-actionable (light blue), or total (orange) mutations per sample per cancer type, and (b) the percentage of samples that carry zero, one, two, or three or more actionable mutations (as defined by OncoKB version October 2022) per sample.
Funding
OncoKB commercial licensing fees
Prostate Cancer Foundation Award
Marie-Josée and Henry R. Kravis Center for Molecular Oncology
National Institutes of Health (NIH)
History
ARTICLE ABSTRACT
There is a continuing debate about the proportion of cancer patients that benefit from precision oncology, attributable in part to conflicting views as to which molecular alterations are clinically actionable. To quantify the expansion of clinical actionability since 2017, we annotated 47,271 solid tumors sequenced with the MSK-IMPACT clinical assay using two temporally distinct versions of the OncoKB knowledge base deployed 5 years apart. Between 2017 and 2022, we observed an increase from 8.9% to 31.6% in the fraction of tumors harboring a standard care (level 1 or 2) predictive biomarker of therapy response and an almost halving of tumors carrying nonactionable drivers (44.2% to 22.8%). In tumors with limited or no clinical actionability, TP53 (43.2%), KRAS (19.2%), and CDKN2A (12.2%) were the most frequently altered genes.
Although clear progress has been made in expanding the availability of precision oncology-based treatment paradigms, our results suggest a continued unmet need for innovative therapeutic strategies, particularly for cancers with currently undruggable oncogenic drivers.See related commentary by Horak and Fröhling, p. 18.This article is featured in Selected Articles from This Issue, p. 5
