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  • Writer's pictureLighthouse
    • 4 min read

RAS Biomarker Trending and Awareness in Oncologists

Updated: Mar 8, 2023

Summary in Thirty Seconds

  • RAS/KRAS was one of the first oncogenes discovered; thus, it provides a strong field for observing various trending and awareness patterns amongst oncologists.

  • The history of KRAS discoveries and treatments strongly tracks with trending and awareness patterns.

  • As clinical trials began for the two KRAS-targeting compounds in 2019, there was little trending or awareness of these compounds.

  • By 2022, trending and awareness were peaking across oncologist groups, most notably in the European academic oncologists for the first FDA-approved KRAS-targeting compound.

  • These findings support previous findings demonstrating that the first approved drug for a given target begins trending earlier and maintains an awareness advantage over its competitor(s) over time because of this head start.

  • Trending and awareness analyses provide a powerful means by which pharmaceutical developers, researchers, and healthcare providers can assess the impact of their efforts on a variety of healthcare disciplines.

RAS/KRAS History

The RAS oncogene was first identified in the early 1980s,[1] which “marked the beginning of molecular oncology in human cancer research.”[2] KRAS represents approximately 90% of the mutated RAS isoforms and is found in almost 90% of pancreatic, 40% of colorectal, and 30% of lung cancers.[3] KRAS mutations are seen in 22% of all analyzed tumors, with HRAS and NRAS mutations occurring at a rate of 3% and 8% respectively.[4] The development and testing of RAS inhibitors had to overcome many hurdles, but a method for arresting cell proliferation was proposed in 2013, opening the door for compound development.[5],[6] The first KRAS (G12C) inhibitor began clinical trials in 2019, leading to FDA approval of sotorasib for NSCLC in 2021, followed by adagrasib in late 2022.


The following image charts the basic timeline of KRAS:[7]

KRAS Trending and Awareness Across Oncologist Groups

This history and timeline provide a context for an analysis of trending and awareness patterns for KRAS for North American and European academic oncologists and community oncologists.


Looking at the parallels between the KRAS timeline and trending shows peaks in trending in 2013-14 when a means to inhibit KRAS was discovered, then peaks for North American and community oncologists when clinical trials began for two KRAS inhibitors, followed by peaks for all three oncologist groups when these inhibitors were approved by the FDA. Notably, European academic oncologists consistently trend higher than the other two oncologist groups. Awareness from 2012-2022 shows a consistent climb for all three groups with European Academic oncologists outpacing the other two groups across the decade of study.


Other RAS/KRAS Biomarker Trending and Awareness

Observing the patterns of trending and awareness for other KRAS/RAS biomarkers yields the following results:

Patterns for community oncologists and North American academic oncologists are very similar, so for the sake of brevity and clarity, community oncologist results are not presented. A peak in NRAS trending is seen in both groups of oncologists in 2014. At about this time, researchers identified NRAS mutations as driving specific cancers, most notably melanoma and AML.[8]


North American academic oncologists had a large peak in trending for the G12C point mutation in 2019 when clinical trials began for the two KRAS inhibitors specifically targeting this mutation. The European academic oncologists showed the beginning of a trending rise in 2019, but this didn’t peak until 2022 after the FDA had approved the two drugs for the treatment of G12C-driven NSCLC. Point mutations G12D and G13D, by comparison, have low levels of trending and awareness across all analyses. Point mutation Q61H is a relatively new target for treatment, and as such, has very low levels of trending and awareness.


Trending and Awareness for KRAS G12C mutation-targeting compounds

Observing trending and awareness patterns for the two KRAS G12C mutation-targeting compounds approved by the FDA (sotorasib and adagrasib) shows that as clinical trials began in 2019, there was little trending or awareness of these compounds. Yet by 2022, trending and awareness were peaking across oncologist groups, most notably in the European academic oncologists for sotorasib. In fact, across the three groups, sotorasib—represented with solid lines—outpaces adagrasib (dotted lines) across all oncology groups measured for both trending and awareness. Sotorasib obtained FDA approval on May 28, 2021; whereas adagrasib’s approval came 1 ½ years later, on December 12, 2022.[9] These findings support previous findings demonstrating that the first approved drug for a given target begins trending earlier and maintains an awareness advantage over its competitor(s) over time because of this head start.


Summary

Given that RAS/KRAS was one of the first oncogenes discovered, it provides a strong field for observing various trending and awareness patterns amongst oncologists. The history of KRAS discoveries and treatments strongly tracks with trending and awareness patterns.


These analyses provide examples of the types of questions or issues that can be addressed through Celerity’s trending and awareness metrics. Without the ability to measure such issues, it would be difficult, if not impossible, to assess the efficacy of compliant awareness efforts, to know how different specific biomarkers or compounds compare to others, or to observe how different groups within a specific discipline (in this case, oncologist groups) vary in their trending and awareness. Trending and awareness reveal the development patterns over time, providing a powerful means by which pharmaceutical developers, researchers, and healthcare providers can assess the impact of their efforts on a variety of healthcare disciplines.

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