# Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer

Source: https://onco.cc/key-papers/paper-arbour-kras-co-mutation-outcomes-ccr-2018/  
OnCo record `paper-arbour-kras-co-mutation-outcomes-ccr-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Among 330 patients whose lung cancer carried a mutated KRAS gene, the ones who also had a broken KEAP1 gene did worse on every treatment: chemotherapy stopped working sooner and immunotherapy barely worked at all.

## Summary

Patients with advanced KRAS-mutant non-small-cell lung cancer were identified and their most common co-occurring genomic alterations evaluated, with multivariate analyses of association with overall survival, response to platinum and pemetrexed chemotherapy and response to immune checkpoint inhibitors. Among 330 patients, the most frequent co-mutations were TP53 (42%), STK11 (29%) and KEAP1 or NFE2L2 (27%). In multivariate analysis, co-mutation in KEAP1 or NFE2L2 carried significantly shorter survival (hazard ratio 1.96), while STK11 (1.3) and TP53 (1.11) co-mutation status were not associated with survival. KEAP1 or NFE2L2 co-mutation was also associated with a shorter duration of initial chemotherapy (hazard ratio 1.64) and shorter overall survival from the start of immune therapy (3.54).

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Clinical Cancer Research
- Year: 2018
- DOI: 10.1158/1078-0432.CCR-17-1841
- Authors: Arbour KC, Jordan E, Kim HR, et al.
- Findings: Commonest co-mutations in KRAS-mutant lung cancer: TP53 42%, STK11 29%, KEAP1 or NFE2L2 27%.; KEAP1 or NFE2L2 co-mutation was an independent predictor of shorter survival, hazard ratio 1.96.; It also shortened the duration of first chemotherapy and survival from the start of immunotherapy.; STK11 and TP53 co-mutation were not independently associated with survival in this model.
- What it means: It separated the prognostic co-mutation, KEAP1, from the predictive one, STK11, in a disease where the two are often quoted together, and it is the reason KEAP1 status is worth reading off a report even though no treatment depends on it.
- Caveats: Single centre and retrospective, with treatment not randomised.; Immunotherapy subgroup numbers are small.; KEAP1 and NFE2L2 were grouped together, so their individual effects cannot be separated.

## Sources

- Arbour et al., Clin Cancer Res 2018: co-occurring alterations and outcomes in 330 KRAS-mutant lung cancers: https://doi.org/10.1158/1078-0432.CCR-17-1841
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29089357/

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [KEAP1](https://onco.cc/targets/keap1/), [KRAS](https://onco.cc/targets/kras/), [NFE2L2](https://onco.cc/targets/nfe2l2/), [STK11](https://onco.cc/targets/stk11/), [TP53](https://onco.cc/targets/tp53/)
- institutions: [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [KEAP1-NRF2 antioxidant pathway](https://onco.cc/pathways/keap1-nrf2/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [T-cell exhaustion](https://onco.cc/pathways/t-cell-exhaustion/)
- terms: [KRAS mutation subtypes (G12C, G12D, G12V)](https://onco.cc/terms/kras-mutation-subtypes/), [STK11 / KEAP1 co-mutations](https://onco.cc/terms/stk11-keap1/)
- people: [Gregory J. Riely](https://onco.cc/people/gregory-riely/)
- journals: [Clinical Cancer Research](https://onco.cc/journals/clinical-cancer-research/)
- biomarkers: [KRAS G12C](https://onco.cc/biomarkers/kras-g12c/), [STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma](https://onco.cc/biomarkers/stk11-keap1-loss/)

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