Biomarkers /
KRAS G12A
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Biomarker-Directed Therapies
KRAS G12A is a predictive biomarker for use of afatinib, dacomitinib, erlotinib, gefitinib, osimertinib, cetuximab, and panitumumab in patients.
Of the therapies with KRAS G12A as a predictive biomarker, 2 are FDA-approved and 7 have NCCN guidelines in at least one clinical setting.
Non-small cell lung carcinoma and colorectal carcinoma have the most therapies targeted against KRAS G12A or its related pathways [5].
Afatinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Cetuximab +
Dacomitinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Erlotinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Gefitinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Osimertinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Clinical Trials
KRAS G12A serves as an inclusion eligibility criterion in 1 clinical trial, of which 1 is open and 0 are closed. Of the trial that contains KRAS G12A as an inclusion criterion, 1 is phase 1 (1 open).
Trials with KRAS G12A in the inclusion eligibility criteria most commonly target non-small cell lung carcinoma, colorectal carcinoma, and pancreatic carcinoma [5].
Kras-targeted long peptide vaccine, capivasertib, dabrafenib, ipilimumab, and nivolumab are the most frequent therapies in trials with KRAS G12A as an inclusion criteria [5].
Significance of KRAS G12A in Diseases
Colorectal Carcinoma +
KRAS G12A is an inclusion criterion in 1 clinical trial for colorectal carcinoma, of which 1 is open and 0 are closed. Of the trial that contains KRAS G12A and colorectal carcinoma as inclusion criteria, 1 is phase 1 (1 open) [5].
Pancreatic Carcinoma +
KRAS G12A is an inclusion criterion in 1 clinical trial for pancreatic carcinoma, of which 1 is open and 0 are closed. Of the trial that contains KRAS G12A and pancreatic carcinoma as inclusion criteria, 1 is phase 1 (1 open) [5].
References
1. Hart R and Prlic A. Universal Transcript Archive Repository. Version uta_20180821. San Francisco CA: Github;2015. https://github.com/biocommons/uta
2. The UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Research. 2019;47:D506-D515.
3. Liu X, Wu C, Li C, and Boerwinkle E. dbNSFP v3.0: A one-stop database of functional predictions and annotations for human nonsynonymous and splice site SNVs. Human Mutation. 2015;37:235-241.
Liu X, Jian X, and Boerwinkle E. dbNSFP: A lightweight database of human nonsynonymous SNPs and their functional predictions. Human Mutation. 2011;32:894-899.
4. The AACR Project GENIE Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discovery. 2017;7(8):818-831. Dataset Version 8. This dataset does not represent the totality of the genetic landscape; see paper for more information.
5. All assertions and clinical trial landscape data are curated from primary sources. You can read more about the curation process here.
