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  • Writer's pictureLighthouse

How Does Awareness of Biomarkers Compare to Prevalence?

Updated: Mar 8, 2023

Summary in Thirty Seconds

  • We compared the awareness of selected biomarkers to the prevalence of these oncogenic mutations across cancers, utilizing prevalence numbers for that of actionable biomarker mutations.

  • Results show that both community and academic oncologists have higher awareness levels for biomarkers with numerous approved drugs compared to the prevalence of these oncogenic mutations.

  • For biomarkers that have fewer approved treatments, prevalence outpaces awareness.

  • Awareness of specified biomarkers appears to be influenced by the length of time that targeted treatments have been available.

  • Academic oncologists have higher levels of awareness for studied biomarkers than community-based oncologists, with some of the low-prevalence biomarkers showing the largest magnitude differences.

Biomarker Awareness and Prevalence

When considering biomarker awareness, an interesting question is how awareness of specific oncogenic biomarkers compares to the prevalence of these biomarkers. We compared the awareness (built over 2012-2022) of selected biomarkers to the prevalence of these oncogenic mutations across cancers. Prevalence data for mutations driving cancers was gathered from MSK’s pan-cancer genomic work[1] and AACR’s Project Genie.[2] We utilized prevalence numbers for that of actionable biomarker mutations rather than overall prevalence (e.g., ROS1 fusions [.3%] rather than all ROS1 mutations/variants [4%]) to show a practical (“real world”) comparison of awareness to the prevalence of cancer-driving variants.


This analysis results in the following graph, with biomarkers arranged chronologically by the year in which a targeted treatment for that biomarker was first FDA-approved:[3]


Awareness vs. Prevalence

This graph shows that both community and academic oncologists have higher awareness levels for biomarkers such as ALK, BRAF, EGFR, and HER2 (ERBB2) compared to the prevalence of these oncogenic mutations. One possible explanation for this split is there are numerous approved drugs (both generally and for targeted treatments) for these biomarkers. In contrast, the prevalence of FGFR, KRAS, and PIK3CA is greater than the awareness levels, and these biomarkers generally have far fewer approved treatments. RET is another mutation with much higher awareness levels than prevalence, particularly for academic oncologists and this may be due to the rarity of actionable RET mutations (i.e., fusions 0.4%) vs. total RET mutations (2-3%). The same pattern for the same reason is seen for NTRK and ROS1.


Awareness by Time of First FDA-Approved Targeted Treatment for Biomarker

Generally, the highest awareness levels for oncologists were related to the length of time that a targeted treatment has been available (e.g., trastuzumab [Herceptin] was first approved for HER2-positive breast cancer in 1998). A notable exception to this pattern is KRAS. Relatively high awareness levels for this biomarker with a more recently approved treatment may be due to the high prevalence rate of KRAS.


Awareness in Community-based vs. Academic Oncologists

When comparing community-based oncologists to academic oncologists, academic oncologists have higher levels of awareness for all the selected biomarkers except for EGFR. It is unclear why community oncologists show higher levels of awareness for this one biomarker. The difference may simply be an artifact of the process by which awareness data is generated. It is also possible that awareness levels are high because there are multiple targeted treatments for EGFR, and one, osimertinib, has shown very strong and well-publicized results leading to high awareness levels and treatment use amongst community oncologists. It also could be that community oncologists have a high awareness of EGFR because it was the first receptor shown to have a relationship between receptor overexpression and cancer[4] and was one of the first biomarkers for which a targeted treatment was FDA-approved.


For biomarkers where academic oncologists have greater awareness than community-based oncologists, some of the low-prevalence biomarkers show the largest magnitude differences. For example, NTRK and ROS1 have large awareness differences; these biomarkers have specific mutations (i.e., fusions), that have been successfully targeted (by two FDA-approved drugs, and a third given breakthrough therapy designation for ROS1). These fusions are identified by Next Generation Sequencing, and research has found that academic oncologists are more likely to use NGS than community-based (or solo practice) oncologists.[5] More frequent NGS use would likely result in higher awareness levels of these fusions in academic vs. community oncologists.


Conclusion

Awareness levels for these specified biomarkers appear to be influenced by the length of time that targeted treatments have been available, with the prevalence of that biomarker influencing awareness, although not as strongly. Generally, academic oncologists have higher levels of awareness for these biomarkers (particularly in rare mutations), possibly because academic oncologists are more frequently involved in clinical trials and work in settings where Next Generation Sequencing (NGS) is more available and used more often. This argues for the importance of consistent (and early) use of NGS in oncology.


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