Abstract
Quantifying the growth of clinical actionability in precision oncology using OncoKB.
Author
person
Sarah P. Suehnholz
Memorial Sloan Kettering Cancer Center, New York, NY
info_outline
Sarah P. Suehnholz, Ritika Kundra, Subhiksha Nandakumar, Moriah H Nissan, Hongxin Zhang, Calvin Lu, Amanda Dhaneshwar, Nicole Fernandez, Stephanie Carrero, Maria E. Arcila, Marc Ladanyi, Michael F. Berger, Aijazuddin Syed, Angela Rose Brannon, Ross L. Levine, Ahmet Dogan, Alexander E. Drilon, David B. Solit, Nikolaus Schultz, Debyani Chakravarty
Full text
Authors
person
Sarah P. Suehnholz
Memorial Sloan Kettering Cancer Center, New York, NY
info_outline
Sarah P. Suehnholz, Ritika Kundra, Subhiksha Nandakumar, Moriah H Nissan, Hongxin Zhang, Calvin Lu, Amanda Dhaneshwar, Nicole Fernandez, Stephanie Carrero, Maria E. Arcila, Marc Ladanyi, Michael F. Berger, Aijazuddin Syed, Angela Rose Brannon, Ross L. Levine, Ahmet Dogan, Alexander E. Drilon, David B. Solit, Nikolaus Schultz, Debyani Chakravarty
Organizations
Memorial Sloan Kettering Cancer Center, New York, NY
Abstract Disclosures
Research Funding
No funding received
None.
Background:
OncoKB (www.oncokb.org), Memorial Sloan Kettering's (MSK) precision oncology knowledge base, contains curated information about the oncogenic effect and therapeutic implications of somatic alterations in cancer and is the first cancer variant database to be partially recognized by the US-FDA. Individual mutations and structural alterations in OncoKB are assigned a level of evidence based on whether the alteration is a predictive biomarker of response or resistance to a genomically matched standard care or investigational drug in a specific cancer subtype. As of February 2023, OncoKB includes annotations for >6200 alterations in >700 cancer-associated genes, including 50 level 1 or 2 standard care genes (specified in the FDA drug label or professional guidelines) as well as 9 level 3A and 12 level 4 genes (predictive of drug response based on well-powered clinical studies or compelling biological evidence, respectively). OncoKB data is used internally to annotate >15,000 MSK patient sequencing reports annually, and its content is integrated into the cBioPortal for Cancer Genomics.
Methods:
To quantitate the expansion of the clinical actionability landscape in precision oncology, we annotated the clinical sequencing results of 47,271 solid tumor samples from the AACR Project GENIE cohort (GENIE 11.0 - public) using two versions of OncoKB, the first from March 2017 and the second from November 2022.
Results:
From 2017 to 2022, we observed a 22.7% increase in the fraction of samples with a standard care biomarker (levels 1 and 2), and a 21.4% decrease in the fraction of samples with a driver alteration that was not clinically actionable. The tumor agnostic approvals of the anti-PD1 antibody pembrolizumab in microsatellite instability high (MSI-H) and tumor mutational burden high (TMB-H) solid tumors resulted in a 11.1%increase of samples with a level 1 biomarker. In sum, of the 38,722 samples across 66 cancer types with limited to no actionability in 2017 (levels 3B, 4 or no level), 21.7% became clinically actionable (levels 1, 2 or 3A) by November 2022. This is an upper bound estimate as it includes samples that may have been eligible for an FDA-approved precision oncology therapy based on cancer subtype alone.
Conclusions:
Our analysis highlights the significant expansion of precision oncology-based therapeutic options for patients with cancer over the past 5 years, as well as the ongoing unmet need for novel precision oncology approaches designed to address oncogenic but not currently actionable drug targets.
Clinical actionability of solid tumor samples from AACR project GENIE cohort.
Highest OncoKB Level of Evidence
OncoKB version
March 2017
OncoKB version
Nov. 2022
Level 1 (including MSI-H)
7.7%
21.0%
Level 1 (only TMB-H)
0%
9.2%
Level 2
1.2%
1.4%
Level 3A
9.2%
4.3%
Level 3B
20.0%
13.6%
Level 4
8.6%
20.6%
Driver without actionability
44.2%
22.8%
No Driver or no alteration
9.1%
7.1%
1 organization
1 drug
1 target
Organization
Memorial Sloan Kettering Cancer CenterDrug
pembrolizumabTarget
PD-1