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Variants & evidence
1,206 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| STK11 Loss5 | ||||||||
| Sirolimus | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | submitted | EID2314STK11 is mutated and inactivated in 20-30% of non-small cell lung cancers, most often in the adenocarcinoma subtype. PMID 15021901 · Carretero et al., 2004 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | rejected | EID2315STK11 is mutated and inactivated in 20-30% of non-small cell lung cancers, most often in the adenocarcinoma subtype. PMID 21102257 · Marcus et al., 2010 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | submitted | EID2316STK11 is mutated and inactivated in 20-30% of non-small cell lung cancers, most often in the adenocarcinoma subtype. PMID 12097271 · Sanchez-Cespedes et al., 2002 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | submitted | EID2317STK11 is mutated and inactivated in 20-30% of non-small cell lung cancers, most often in the adenocarcinoma subtype. PMID 18948947 · Ding et al., 2008 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID2313NSCLC cell lines that contain inactivating STK11 mutations and activating KRAS mutations have shown a reduced proliferation rate in response to the MEK inhibitor CI-1040 (P<0.001) compared to NSCLC ce… (full text at CIViC) PMID 19165201 · Mahoney et al., 2009 · Open in CIViC | civic |
| STK11 Mutation5 | ||||||||
| Chemoradiotherapy | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID12911In a retrospective cohort of stage III NSCLC treated with definitive radiotherapy with or without concurrent chemotherapy (n = 164), somatic STK11 (LKB1) mutations (n = 12) were associated with higher… (full text at CIViC) PMID 33323404 · Sitthideatphaiboon et al., 2021 · Open in CIViC | civic |
| Cisplatin/Pembrolizumab/Pemetrexed Regimen | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 4 | submitted | EID12338A retrospective analysis of 871 non-squamous NSCLC patients treated with chemotherapy (platinum compound plus pemetrexed) combined with immunotherapy (pembrolizumab) found that those with STK11 mutati… (full text at CIViC) PMID 39385035 · Skoulidis et al., 2024 · Open in CIViC | civic |
| Atezolizumab | ||||||||
| KEAP1 Mutation + STK11 MutationSTK11KEAP11 | ||||||||
| Cisplatin/Pembrolizumab/Pemetrexed Regimen | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | submitted | EID12340A retrospective analysis of 871 non-squamous NSCLC patients treated with chemotherapy (platinum compound plus pemetrexed) combined with immunotherapy (pembrolizumab) found that those with STK11 or KEA… (full text at CIViC) PMID 39385035 · Skoulidis et al., 2024 · Open in CIViC | civic |
| KEAP1 G417W + STK11 Rearrangement exon 1STK11KEAP11 | ||||||||
| Chemoimmunotherapy + Palliative Radiation TherapySequential | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Resistance | 2 | submitted | EID12933In a case report of KRAS wild‑type NSCLC (n = 1, age 53 male) a tumor harbored concurrent STK11 (rearrangement exon 1) and KEAP1 (G417W) mutations, along with additional somatic alterations (including… (full text at CIViC) PMID 36858519 · Sumii et al., 2023 · Open in CIViC | civic |
| H-bTMB1 | ||||||||
| Immune Checkpoint Inhibitor | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12724The use of circulating tumor DNA in blood for TMB assessment was tested. The cancer gene panel NCC-GP150, which covers the whole exon regions of 150 genes, was created and tested for correlation again… (full text at CIViC) PMID 30816954 · Wang et al., 2019 · Open in CIViC | civic |
| High15 | ||||||||
| Atezolizumab | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12587This retrospective study evaluated the clinical utility of blood tumour mutational burden (bTMB) as a predictive biomarker for atezolizumab efficacy in advanced non-small cell lung cancer (NSCLC) who … (full text at CIViC) PMID 30082870 · Gandara et al., 2018 · Open in CIViC | civic |
| Chemotherapy + ToripalimabCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12798This is part of a multi-centred, randomised, placebo-controlled phase 3 trial, CHOICE-01, that examined therapeutic response to first-line chemotherapy plus PD-1 inhibitor in non-small cell lung cance… (full text at CIViC) PMID 39255777 · Xu et al., 2024 · Open in CIViC | civic |
| Durvalumab | ||||||||
| Low on-treatment bTMB1 | ||||||||
| Camrelizumab + Carboplatin/Paclitaxel RegimenCombination | Lung Squamous Cell Carcinoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12919This is part of the randomised double-blind phase 3 trial, CameL-sq, a study that assessed the therapeutic effectiveness of the PD-1 blockade, camrelizumab plus chemotherapy as first-line treatment in… (full text at CIViC) PMID 34980131 · Jiang et al., 2022 · Open in CIViC | civic |
| TP53 Deleterious Mutation2 | ||||||||
| (prognostic) | Lung Non-Small Cell CarcinomaCURATED_BROADER | Prognostic | B | Does Not Support Poor Outcome | 4 | accepted | EID1147Pooled analysis of TP53 mutations (exons 5-8) from 4 randomized trials (IALT, JBR10, CALGB-9633 and ANITA). Mutations (434; 36%) had no prognostic effect (OBS: HROS=0.99; [95%CI 0.77-1.28], p=0.95; HR… (full text at CIViC) PMID 26899019 · Ma et al., 2016 · Open in CIViC | civic |
| Adjuvant Chemotherapy | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 2 | accepted | EID1148Pooled analysis of TP53 mutations (exons 5-8) from 4 randomized trials (IALT, JBR10, CALGB-9633 and ANITA) of platinum-based adjuvant chemotherapy (ACT) versus observation (OBS). Patients with TP53wt … (full text at CIViC) PMID 26899019 · Ma et al., 2016 · Open in CIViC | civic |
| TP53 Loss1 | ||||||||
| Docetaxel | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | accepted | EID1146A clinical trial comparing selumetinib and docetaxel vs. docetaxel and placebo in KRAS mutant NSCLC was recapitulated in mice. Tumors were induced in lung epithelium by nasal instillation of CRE-beari… (full text at CIViC) PMID 22425996 · Chen et al., 2012 · Open in CIViC | civic |
| TP53 Mutation4 | ||||||||
| (prognostic) | Lung Non-Small Cell CarcinomaCURATED_BROADER | Prognostic | B | Supports N/A | 5 | accepted | EID2999A pooled analysis to investigate the prognostic and predictive roles of TP53/KRAS and TP53/EGFR comutations (cm) in randomized trials of adjuvant chemotherapy compared to observational therapy encompa… (full text at CIViC) PMID 28453411 · Shepherd et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID6031In an analysis of 321 patients with lung adenocarcinoma who received potentially curative pulmonary resection, patients with TP53 mutated tumors (N=115, exons 4-10 evaluated) had significantly poorer … (full text at CIViC) PMID 19096302 · Kosaka et al., 2009 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Prognostic | B | Supports | ||||
| TP53 Wildtype1 | ||||||||
| Adjuvant Chemotherapy | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1149Pooled analysis of TP53 mutations (exons 5-8) from 4 randomized trials (IALT, JBR10, CALGB-9633 and ANITA, 1209 patients, median follow-up 5.5 years) of platinum-based adjuvant chemotherapy (ACT) vers… (full text at CIViC) PMID 26899019 · Ma et al., 2016 · Open in CIViC | civic |
| NTRK1 Fusion1 | ||||||||
| Larotrectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID11744In the clinical trial NCT01775072, one patient had TPR::NTRK1 positive non-small cell lung cancer, and had a partial response with larotrectinib treatment before eventual progression. PMID 33004339 · Cocco et al., 2021 · Open in CIViC | civic |
| TTF1 AMPLIFICATION1 | ||||||||
| (prognostic) | Lung Adenocarcinoma | Prognostic | B | Does Not Support N/A | 3 | accepted | EID5276 of 89 patients with lung adenocarcinoma had amplification of TTF1. There was no statistical difference in overall survival between patients with and without gene amplification. PMID 19040416 · Barletta et al., 2009 · Open in CIViC | civic |
| TYMS Amplification1 | ||||||||
| Pemetrexed | Lung Adenocarcinoma | Predictive | B | Supports Resistance | 3 | accepted | EID903TYMS copy number was lower in clinical samples responding to pemetrexed in combination with platinum (n=25). The same was found in 17 cell lines. PMID 23645741 · Kasai et al., 2013 · Open in CIViC | civic |
| TYMS Overexpression2 | ||||||||
| Pemetrexed | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID832mRNA expression of thymidylate synthase (TYMS) in 62 NSCLC patients correlated with response rate to pemetrexed mono- or combination therapy. Response rate with low TYMS expression was 0.29 compared w… (full text at CIViC) PMID 26502926 · Chamizo et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID922mRNA levels of TYMS, DHFR and GARFT were assessed (rt-PCR) in 50 patient samples of NSCLC. TYMS mRNA levels were lower in responders compared to non-responders to pemetrexed (1.671 ± 0.844 versus 5.97… (full text at CIViC) PMID 23060591 · Shimizu et al., 2012 · Open in CIViC | civic |
| TYMS Underexpression1 | ||||||||
| Pemetrexed | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID90749 tumor specimens from 268 NSCLC patients treated with pemetrexed were evaluated for expression of TYMS and DHFR by IHC and compared to treatment outcomes. Patients with low TS (≤150) expression had … (full text at CIViC) PMID 21367480 · Chen et al., 2011 · Open in CIViC | civic |
| ALK Fusion7 | ||||||||
| Alectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1282In this Phase II trial of 87 patients (NCT01871805), alectinib was assayed for safety and efficacy in ALK positive NSCLC that had progressed on crizotinib. Of 69 patients with measurable disease, 35 a… (full text at CIViC) PMID 26708155 · Shaw et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID7284In a phase 3 trial, 303 patients with NSCLC with ALK fusion were randomly assigned to alectinib arm (N=152) or crizotinib arm (N=151). PFS was significantly longer with alectinib than with crizotinib … (full text at CIViC) PMID 28586279 · Peters et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell Carcinoma | |||||||
Data updated 14 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| Lung Adenocarcinoma |
| Predictive |
| B |
| Supports Resistance |
| 4 |
| accepted |
EID6441In a retrospective analysis in two separate datasets (Stand Up To Cancer 2 Cohort and Checkmate-057), patients with concomitant KRAS and STK11 mutations had significantly worse response rates, PFS and… (full text at CIViC) PMID 29773717 · Skoulidis et al., 2018 · Open in CIViC |
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| Radiation Therapy | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 4 | submitted | EID12912In retrospective analyses of multiple non‑metastatic NSCLC cohorts (TCGA PanCancer n = 736, MSK‑IMPACT n = 961, TRACERx n = 100), pathogenic STK11 mutations were associated with worse outcomes only in… (full text at CIViC) PMID 35958336 · Kinslow et al., 2022 · Open in CIViC | civic |
| Vistusertib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 2 | accepted | EID12514In a phase II trial of 49 NSCLC patients with STK11 mutation, the MTORC1/2 inhibitor vistusertib did not result in any responses. PMID 40069402 · Middleton et al., 2025 · Open in CIViC | civic |
| Lung Non-Small Cell CarcinomaCURATED_BROADER |
| Predictive |
| B |
| Does Not Support Sensitivity Response |
| 3 |
| accepted |
EID12799This is part of a open-label phase 3 trial, NEPTUNE, that examined therapeutic response to first-line durvalumab plus tremelimumab in patients with metastatic non-small cel lung cancer (NSCLC). 823 pa… (full text at CIViC) PMID 36240972 · de Castro et al., 2023 · Open in CIViC |
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| Durvalumab/Tremelimumab Regimen | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 5 | accepted | EID12822The MYSTIC study compared response rates for immunotherapy verses chemotherapy. Specifically looking at the efficacy of the anti-PD-L1 therapy, durvalumab, with/without the anti-CTLA-4 therapy, tremel… (full text at CIViC) PMID 33355200 · Si et al., 2021 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID12760This exploratory analysis of the Phase 3 MYSTIC trial (NCT02453282) evaluated blood tumour mutational burden (bTMB) as a predictive biomarker for first-line durvalumab with or without tremelimumab vs … (full text at CIViC) PMID 32271377 · Rizvi et al., 2020 · Open in CIViC | civic |
| Immune Checkpoint Inhibitor | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID13061This retrospective study evaluated the predictive value of tumor mutational burden (TMB) for immune checkpoint inhibitor (ICI) outcomes in 97 patients with stage IV non-small cell lung cancer who had … (full text at CIViC) PMID 38950679 · Di Federico et al., 2024 · Open in CIViC | civic |
| Immunotherapy | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID13032A retrospective cohort study was performed with advanced NSCLC patients who had prior immunotherapy with available genomic testing, and TMB determined by NGS via the Foundation Medicine assay. 87 pati… (full text at CIViC) PMID 33972172 · Kao et al., 2021 · Open in CIViC | civic |
| Ipilimumab/Nivolumab Regimen | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | rejected | EID12612This part of the open-label multipart phase 3 trial, CheckMate 277 (Trial ID: 29658845), examined the performance of nivolumab plus ipilimumab compared to chemotherapy among non-small-cell lung cancer… (full text at CIViC) PMID 29658845 · Hellmann et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12614This part of the open-label multipart phase 3 trial, CheckMate 277 (Trial ID: 29658845), examined the performance of nivolumab plus ipilimumab compared to chemotherapy among non-small-cell lung cancer… (full text at CIViC) PMID 29658845 · Hellmann et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID13103Whole-exome sequencing-derived tumor mutational burden (TMB) was obtained from 75 patients recruited as part of the the CheckMate-012 trial (phase 1, open label, multicenter clincal trial of nivolumab… (full text at CIViC) PMID 29657128 · Hellmann et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID12588This retrospective analysis assessed the association between tumor mutational burden (TMB) and the efficacy of nivolumab plus low-dose ipilimumab as first-line treatment for advanced/metastatic non-sm… (full text at CIViC) PMID 30785829 · Ready et al., 2019 · Open in CIViC | civic |
| Nivolumab | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12967In an exploratory analysis of the phase III CheckMate 026 trial in previously untreated stage IV or recurrent non-small-cell lung cancer, patients with high tumor mutational burden (≥243 missense muta… (full text at CIViC) PMID 28636851 · Carbone et al., 2017 · Open in CIViC | civic |
| PD1 Inhibitor + PD-L1 InhibitorSubstitutes | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12586High Tumor Mutation Burden (TMB >19 mutations/Mb) represents a robust and platform-validated genomic biomarker predictive of clinical benefit from PD-1/PD-L1 immune checkpoint blockade in non–small ce… (full text at CIViC) PMID 35708671 · Ricciuti et al., 2022 · Open in CIViC | civic |
| Pembrolizumab | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12083Exomes were sequenced from two cohorts of non small cell lung cancer patients who were treated with pembrolizumab. In a discovery cohort of 16 patients, durable clinical benefit (DCB - partial or stab… (full text at CIViC) PMID 25765070 · Rizvi et al., 2015 · Open in CIViC | civic |
| Pembrolizumab/Pemetrexed Regimen | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 3 | accepted | EID12851This analysis of the Phase 2 KEYNOTE-782 trial (NCT03664024) evaluated the correlation of blood tumor mutational burden (bTMB) with the efficacy of first-line pembrolizumab plus platinum-based chemoth… (full text at CIViC) PMID 38422883 · Bar et al., 2024 · Open in CIViC | civic |
| 3 |
| submitted |
EID6032Analysis of 135 patients with chemotherapy naive lung adenocarcinoma, TP53 mutations were associated with reduced progression free survival (p = 0.0014, log rank test) using primary resection specimen… (full text at CIViC) PMID 22980975 · Imielinski et al., 2012 · Open in CIViC |
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| Docetaxel + SelumetinibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1145A clinical trial comparing selumetinib and docetaxel vs. docetaxel and placebo in KRAS mutant NSCLC was recapitulated in mice. Tumors were induced in lung epithelium by nasal instillation of CRE-beari… (full text at CIViC) PMID 22425996 · Chen et al., 2012 · Open in CIViC | civic |
| Predictive |
| A |
| Supports Sensitivity Response |
| 5 |
| submitted |
EID7533In this phase II study the safety, efficacy, and pharmacokinetics of twice daily 600mg alectinib treatment was assessed in 138 patients with advanced NSCLC harboring ALK rearrangements (previously det… (full text at CIViC) PMID 26598747 · Ou et al., 2016 · Open in CIViC |
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| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | submitted | EID7872National Comprehensive Cancer Network (NCCN) guidelines recommend alectinib for advanced ALK-positive NSCLC who are previously untreated or previously treated with crizotinib, including those with bra… (full text at CIViC) PMID 30030733 · Paik et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID8657A randomized phase 3 trial (J-ALEX) of 207 Japanese ALK-positive NSCLC patients compared the efficacy and safety of alectinib (300mg twice daily) and crizotinib (250mg twice daily) in the first-line s… (full text at CIViC) PMID 28501140 · Hida et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID12012In this global phase 3 trial, 257 patients with ALK-positive Non-Small-Cell Lung Cancer were treated with either alectinib (n = 130) or chemotherapy (n = 127). 93.8 % of the patients who had received … (full text at CIViC) PMID 38598794 · Wu et al., 2024 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1279In this Phase I trial (NCT01588028) in 47 patients, alectinib was assessed for its effectiveness in treating locally advanced or metastatic ALK-positive NSCLC that had progressed or been resistant to … (full text at CIViC) PMID 25153538 · Gadgeel et al., 2014 · Open in CIViC | civic |