Skip to content

How real-world data was used to assess the prognostic value of co-occurring genomic alterations


August 2022

Flatiron Health and Foundation Medicine Clinico-Genomic Database

Unmet Need
Natural History

Metastatic Non-Small Cell Lung Cancer



Immunotherapy and Chemotherapy


The clinical implications of co-occurring genomic alterations in patients with cancer has emerged as a prominent area of study for precision oncology 1, particularly their predictive and prognostic capacities. While novel diagnostics and personalized medicine 2 have led to major advances in oncology therapeutics, some patients still do not benefit from these targeted therapies. For example, in metastatic non-small cell lung cancer (NSCLC), actionable alterations such as ALK, EGFR and ROS-1 have been extensively studied, while co-occurring alterations 3 are just now emerging as an opportunity to maximize clinical benefit from personalized therapies.

In clinical trials, STK11 mutations alone or co-occurring with KRAS mutations have been associated with poor survival outcomes for patients with metastatic NSCLC undergoing immunotherapy or chemotherapy treatment. However, limited data were previously available on the prognostic value of STK11 and KRAS/STK11 mutations in patients being treated in a real-world setting — in other words, outside of clinical trials.

In a study led by AstraZeneca, a nationwide (US-based) de-identified Flatiron Health-Foundation Medicine NSCLC clinico-genomic database (FH-FMI CGDB) was used to examine the prevalence of STK11 mutations, KRAS/STK11 co-mutations, and clinical outcomes associated with those mutations were assessed in 2,407 patients with metastatic NSCLC who were receiving first-line or second-line immunotherapy or chemotherapy. The inclusion of information on alteration status for >300 genes from the FoundationOne comprehensive genomic profiling assay (including KRAS and STK11), which is included in the CGDB, uniquely enabled this type of analysis as STK11 is not routinely assessed in current real-world clinical practice.

In this natural history study, the researchers assessed

The AstraZeneca study found that patients with STK11 mutations had worse real-world overall survival and

The CGDB can be used to assess the prognostic value of novel biomarkers alone or in combination to corroborate clinical trial results in a real world population and identify patients who may benefit from additional treatment options. Future natural history studies using the CGDB could assess unmet medical needs and prioritize targetable alterations for future therapy development.

Learn more about our oncology real-world evidence solutions

Interested in seeing how Flatiron’s RWE solutions transform the possibilities of oncology research, development, and commercialization?


Shire NJ, Klein AB, Golozar A, Collins JM, Fraeman KH, et al. (2020) STK11 (LKB1) mutations in metastatic NSCLC: Prognostic value in the real world. PLOS ONE 15(9): e0238358.

1 Mateo, L., Duran-Frigola, M., Gris-Oliver, A. et al. Personalized cancer therapy prioritization based on driver alteration co-occurrence patterns. Genome Med 12, 78 (2020).

2 Krzyszczyk P, Acevedo A, Davidoff EJ, et al. The growing role of precision and personalized medicine for cancer treatment. Technology (Singap World Sci). 2018;6(3-4):79-100. doi:10.1142/S2339547818300020

3 Skoulidis F, Heymach JV. Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy. Nat Rev Cancer. 2019;19(9):495-509. doi:10.1038/s41568-019-0179-8