Evidence map›Paper›PMID 39037971›Full record

ArticlePloS one2024

Effects of KRAS, STK11, KEAP1, and TP53 mutations on the clinical outcomes of immune checkpoint inhibitors among patients with lung adenocarcinoma.

Yao Liang, Osamu Maeda, Chiaki Kondo, Kazuki Nishida, Yuichi Ando

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Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Yao LiangDepartment of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Aichi, Japan.ORCID 0009-0005-2365-1513
Osamu MaedaDepartment of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Aichi, Japan.
Chiaki KondoDepartment of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Aichi, Japan.
Kazuki NishidaDepartment of Advanced Medicine, Nagoya University Hospital, Nagoya, Aichi, Japan.
Yuichi AndoDepartment of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Aichi, Japan.ORCID 0000-0002-6849-2297

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThis study aimed to identify the associations between individual KRAS, STK11, KEAP1, or TP53 mutations, as well as the comutation status of these genes, and the tumor mutation burden (TMB) with clinical outcomes of lung adenocarcinoma patients treated with immune checkpoint inhibitors (ICIs).

methodsWe collected data from patients with lung adenocarcinoma treated with ICIs from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database between June 2019 and August 2023. The main endpoints were the treatment response and overall survival (OS).

resultsAmong 343 patients with lung adenocarcinoma, 61 (18%), 69 (20%), 41 (12%), and 222 (65%) patients had KRAS, STK11, KEAP1, and TP53 mutations, respectively. An overall objective response was observed in 94 of 338 patients (28%), including 2 (1%) who achieved a complete response and 92 (27%) who achieved a partial response. Patients with STK11, KEAP1, or TP53 mutations had a significantly greater TMB (P<0.001). According to the univariate analysis, the treatment response was significantly correlated with TP53 mutation in both the general (P = 0.041) and KRAS wild-type (P = 0.009) populations. KEAP1 and TP53 mutations were associated with worse OS among assessable patients (hazard ratio (HR) = 2.027, P = 0.002; HR = 1.673, P = 0.007, respectively) and among patients without KRAS mutations (HR = 1.897, P = 0.012; HR = 1.908, P = 0.004, respectively). According to the multivariate analysis, KEAP1 (HR = 1.890, P = 0.008) and TP53 (HR = 1.735, P = 0.011) mutations were found to be independent factors for OS.

conclusionsSTK11, KEAP1, and TP53 mutations are significantly associated with a high TMB. TP53 mutation could affect the treatment response to some degree, and both KEAP1 and TP53 mutations resulted in inferior OS in the general patient population and in those with KRAS-wild-type lung adenocarcinoma, indicating that KEAP1 and TP53 mutations might act as prognostic factors for ICI treatment in lung adenocarcinoma patients.

Indexed as

Adenocarcinoma of LungAMP-Activated Protein Kinase KinasesImmune Checkpoint InhibitorsKelch-Like ECH-Associated Protein 1Lung NeoplasmsMutationProtein Serine-Threonine KinasesProto-Oncogene Proteins p21(ras)Tumor Suppressor Protein p53AdultAgedAged, 80 and overFemaleHumansMaleMiddle AgedAMP-Activated Protein Kinase KinasesImmune Checkpoint InhibitorsKEAP1 protein, humanKelch-Like ECH-Associated Protein 1KRAS protein, humanProtein Serine-Threonine KinasesProto-Oncogene Proteins p21(ras)STK11 protein, humanTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID39037971
PMCPMC11262633

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.