# Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies

Source: https://onco.cc/key-papers/paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017/  
OnCo record `paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Sequencing 860 patients with advanced lung adenocarcinoma as they arrived in clinic answered a question nobody had measured: how many of them actually get a treatment because of the test. Just over a third did.

## Summary

Eight hundred and sixty patients with metastatic lung adenocarcinoma were analysed prospectively for mutations in more than 300 cancer-associated genes. Potentially actionable genetic events were stratified into four levels by the published evidence that the alteration confers sensitivity to a standard or investigational therapy. Overall, 319 of 860 patients, 37.1%, received a matched therapy guided by the molecular profile. Excluding alterations already associated with standard-of-care therapy, 69 of 478 patients, 14.4%, received matched therapy, with clinical benefit in 52% of them. Use of matched therapy was strongly influenced by the level of pre-existing evidence that the alteration predicts drug response. Analysis of genes mutated significantly more often in tumours without a known actionable alteration nominated STK11 and KEAP1 as possible targetable mitogenic drivers.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Cancer Discovery
- Year: 2017
- DOI: 10.1158/2159-8290.CD-16-1337
- Authors: Jordan EJ, Kim HR, Arcila ME, et al.
- Findings: 37.1% of prospectively sequenced patients received a therapy matched to the result.; Outside standard-of-care alterations, 14.4% received a matched therapy, with benefit in 52%.; The level of published evidence, not the presence of the alteration, determined whether treatment followed.; STK11 and KEAP1 emerged as the recurrent alterations in tumours with no other actionable driver.
- What it means: It is the honest accounting of precision oncology in the disease where it works best: broad sequencing changes treatment for about one patient in three, and the bottleneck is evidence rather than detection.
- Caveats: A single referral centre with early access to trials, so the matched-therapy rate is a ceiling rather than an average.; Benefit was assessed without a control group.; Panel sequencing, so fusion and copy-number detection depend on the panel's design.

## Sources

- Jordan et al., Cancer Discov 2017: prospective molecular characterisation of 860 metastatic lung adenocarcinomas (MSK-IMPACT): https://doi.org/10.1158/2159-8290.CD-16-1337
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28336552/
- cBioPortal study lung_msk_2017 (MSK, Cancer Discov 2017; 915 MSK-IMPACT samples from the 860 prospectively sequenced metastatic lung adenocarcinomas): https://www.cbioportal.org/study/summary?id=lung_msk_2017

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/)
- targets: [ALK](https://onco.cc/targets/alk/), [BRAF](https://onco.cc/targets/braf/), [EGFR](https://onco.cc/targets/egfr/), [HER2](https://onco.cc/targets/her2/), [KEAP1](https://onco.cc/targets/keap1/), [KRAS](https://onco.cc/targets/kras/), [MET](https://onco.cc/targets/met/), [RET](https://onco.cc/targets/ret/), [ROS1](https://onco.cc/targets/ros1/), [STK11](https://onco.cc/targets/stk11/)
- institutions: [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [Non-small cell lung cancer (KEGG map)](https://onco.cc/pathways/nsclc-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- terms: [Driver mutation](https://onco.cc/terms/driver-mutation/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/), [STK11 / KEAP1 co-mutations](https://onco.cc/terms/stk11-keap1/)
- people: [Gregory J. Riely](https://onco.cc/people/gregory-riely/)
- journals: [Cancer Discovery](https://onco.cc/journals/cancer-discovery/)

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