Histology
Carcinoma of Unknown Primary
CI-CAN-00002109Explore in graph →
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Histology
CI-CAN-00002109Explore in graph →
Variants & evidence
1,033 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 |
|---|---|---|---|---|---|---|---|---|
| EGFR K757R1 | ||||||||
| Erlotinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1786In a meta-analysis of 7 clinical trials evaluating the efficacy of erlotinib, one patient was described with the exon 19 mutation K757R from the MERIT study. Progression-free (250 days) and overall (4… (full text at CIViC) PMID 26773740 · Klughammer et al., 2016 · Open in CIViC | civic |
| EGFR L718Q2 | ||||||||
| Erlotinib + OsimertinibCombination | Lung Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID8081A genetically engineered mouse model of lung adenocarcinoma (LUAD) was created expressing human EGFR L858R transgene. A set of osimertinib resistant tumours were treated with 25mg/kg osimertinib and 2… (full text at CIViC) PMID 32193290 · Starrett et al., 2020 · Open in CIViC | civic |
| Osimertinib | Lung Adenocarcinoma | Predictive | D | Supports Resistance | 4 | submitted | EID8058A genetically engineered mouse model of lung adenocarcinoma (LUAD) was created expressing human EGFR L858R transgene. Mice were treated with either daily 5mg/kg, followed by 25mg/kg after tumour recur… (full text at CIViC) PMID 32193290 · Starrett et al., 2020 · Open in CIViC | civic |
| EGFR L718Q + EGFR L718V2 | ||||||||
| Afatinib | Lung Adenocarcinoma | Predictive | C | Does Not Support Resistance | 3 | submitted | EID8054A 62 year old patient with 4 pack-year smoking history with back and flank pain was found to have metastatic lung adenocarcinoma by CT and MRI. Targeted NGS sequencing discovered an EGFR L858R mutatio… (full text at CIViC) PMID 32193290 · Starrett et al., 2020 · Open in CIViC | civic |
| Osimertinib | Lung Adenocarcinoma | Predictive | C | Supports Resistance | 4 | submitted | EID8052A 62 year old patient with 4 pack-year smoking history with back and flank pain was found to have metastatic lung adenocarcinoma by CT and MRI. Targeted NGS sequencing discovered an EGFR L858R mutatio… (full text at CIViC) PMID 32193290 · Starrett et al., 2020 · Open in CIViC | civic |
| EGFR L718V2 | ||||||||
| Erlotinib | Lung Adenocarcinoma | Predictive | D | Supports Resistance | 2 | submitted | EID8069Preclinical models of osimertinib-resistant EGFR mutants were treated with erlotinib or afatinib. Treatment with erlotinib suppressed phosphorylation of EGFR L858R+C797S but did not decrease phosphory… (full text at CIViC) PMID 32193290 · Starrett et al., 2020 · Open in CIViC | civic |
| Osimertinib | Lung Adenocarcinoma | Predictive | D | Supports Resistance | 3 | submitted | EID8059A genetically engineered mouse model of lung adenocarcinoma (LUAD) was created expressing human EGFR L858R transgene. Mice were treated with either daily 5mg/kg, followed by 25mg/kg after tumour recur… (full text at CIViC) PMID 32193290 · Starrett et al., 2020 · Open in CIViC | civic |
| EGFR L747_P753delinsS2 | ||||||||
| Erlotinib | Pancreatic Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID6005Patients with recurrent pancreatic adenocarcinoma was treated with gemcitabine + nab-paclitaxel, FOLFIRINOX and docetaxel + irinotecan. After failure of these treatment, a tumor specimen from the panc… (full text at CIViC) PMID 28874593 · Cecchini et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | — | submitted | EID4270In a retrospective study of 46 Caucasian, advanced lung adenocarcinoma patients, a patient harboring EGFR L747_P753insS mutation was associated with resistance to erlotinib treatment. The patient surv… (full text at CIViC) PMID 27032107 · De Grève et al., 2016 · Open in CIViC | civic |
| EGFR L747_S752delinsQ1 | ||||||||
| Erlotinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID4667EGFR exons 18-24 were analyzed in 7 patients who had shown a partial response to erlotinib in a phase II trial for bronchioloalveolar carcinoma (BAC, or in situ pulmonary adenocarcinoma). One patient … (full text at CIViC) PMID 15329413 · Pao et al., 2004 · Open in CIViC | civic |
| EGFR L792H1 | ||||||||
| Osimertinib | Lung Adenocarcinoma | Predictive | D | Supports Resistance | 2 | submitted | EID8079A genetically engineered mouse model of lung adenocarcinoma (LUAD) was created expressing human EGFR L858R+T790M transgene. Twenty of 49 mice treated with osimertinib developed treatment-resistant tum… (full text at CIViC) PMID 32193290 · Starrett et al., 2020 · Open in CIViC | civic |
| EGFR H835L + EGFR L833V1 | ||||||||
| Firmonertinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID13093Two patients with advanced lung adenocarcinoma harboring the EGFR L833V/H835L compound mutation received first-line furmonertinib (80 mg once daily), and both achieved partial responses according to R… (full text at CIViC) PMID 40963567 · Wang et al., 2025 · Open in CIViC | civic |
| EGFR L858R13 | ||||||||
| (oncogenic) | Lung Adenocarcinoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID13025In this preclinical study, expression of EGFR L858R in Ba/F3 cells induced interleukin-3-independent proliferation, demonstrating ligand-independent cellular transformation. EGFR L858R was constitutiv… (full text at CIViC) PMID 16204070 · Jiang et al., 2005 · Open in CIViC | civic |
| Afatinib | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID879A phase III clinical trial (NCT00949650) found that median progression free survival among patients with exon 19 deletions or L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months… (full text at CIViC) PMID 23816960 · Sequist et al., 2013 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | ||
| EGFR L858R + EGFR T790M + MET Exon 14 Skipping MutationEGFRMET1 | ||||||||
| Tepotinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID11486A 76-year old woman (non-smoker) presented with stage IVB ling adenocarcinoma. Genetic testing was positive for EGFR L858R and T790M and osimertinib was given. Partial response was noted until progres… (full text at CIViC) PMID 36313664 · Takamori et al., 2022 · Open in CIViC | civic |
| EGFR L858R + EGFR T790M + EGFR Fusion1 | ||||||||
| Osimertinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID12549A 67 year old female with stage IIIA lung adenocarcinoma had right lobectomy followed by 4 cycles adjuvant chemotherapy with pemetrexed and cisplatin. Next generation sequencing (NGS) found EGFR L858R… (full text at CIViC) PMID 35004270 · Wang et al., 2021 · Open in CIViC | civic |
| EGFR Exon 19 Deletion + EGFR L858R1 | ||||||||
| Erlotinib | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID3791The phase 3 (EURTAC) study consisted of of 173 non-small cell lung cancer patients who had not had prior chemotherapy for metastatic disease (although adjuvant or neoadjuvant chemotherapy was permitte… (full text at CIViC) PMID 22285168 · Rosell et al., 2012 · Open in CIViC | civic |
| EGFR L861Q1 | ||||||||
| Afatinib | Esophageal Squamous Cell CarcinomaALIAS | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID9679This retrospective preclinical study assessed the efficacy of afatinib towards esophageal squamous cell carcinoma (ESCC) cell lines expressing EGFR L861Q mutation. In one experiment, a ESCC KYSE270 EG… (full text at CIViC) PMID 27207775 · Nakamura et al., 2016 · Open in CIViC | civic |
| EGFR L861R1 | ||||||||
| Crizotinib | Lung Adenocarcinoma | Predictive | C | Supports Resistance | — | submitted | EID4300In a patient with metastatic adenocarcinoma of the lung harboring EGFR L861R mutation, MET D1028H and EGFR amplification, EGFR L861R was associated with acquired resistance to crizotinib monotherapy. … (full text at CIViC) PMID 26845121 · Benderra et al., 2016 · Open in CIViC | civic |
| MACF1 Fusion1 | ||||||||
| Aumolertinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID12365A 65-year-old female with lung adenocarcinoma underwent NGS testing, revealing an EGFR-MACF1 fusion at the RNA level (mutation abundance: 17%) and EGFR amplification (copy number: 24.15). The fusion i… (full text at CIViC) PMID 38595815 · Wang et al., 2024 · Open in CIViC | civic |
| EGFR Mutation4 | ||||||||
| (prognostic) | Lung Adenocarcinoma | Prognostic | B | Supports Better Outcome | 4 | accepted | EID1701In a study of 1036 patients with lung adenocarcinomas, patients with EGFR mutations (n=275) showed better prognosis (OS: 34 months versus 23 months; HR=0.6; P<0.001). PMID 22810899 · Johnson et al., 2013 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Prognostic | B | Supports Better Outcome | 3 | accepted | EID3792Analysis was performed on the placebo group (n=451) of the Phase III study SATURN using erlotinib maintenance therapy for patients with advanced NSCLC who were selected for response or stable disease … (full text at CIViC) PMID 21969500 · Brugger et al., 2011 · Open in CIViC | civic |
| Gefitinib | Lung Adenocarcinoma | Predictive | C | Does Not Support Reduced Sensitivity | 3 | submitted | ||
| EGFR Mutation + YES1 AmplificationEGFRYES11 | ||||||||
| Afatinib | Lung Adenocarcinoma | Predictive | D | Supports Resistance | 3 | rejected | EID12094A transposon mutagenesis screen for resistance to a second-generation TKI afatinib was performed in EGFR-TKI sensitive PC9 lung adenocarcinoma cell line that harbours exon 19 EGFR deletion. YES1 was f… (full text at CIViC) PMID 29875142 · Fan et al., 2018 · Open in CIViC | civic |
| EGFR N771delinsVH1 | ||||||||
| Erlotinib | Lung Adenocarcinoma | Predictive | C | Supports Resistance | — | submitted | EID4796In a retrospective study of 46 Caucasian, advanced lung adenocarcinoma patients, a patient harboring EGFR N771insVH mutation was associated with resistance to erlotinib treatment. The patient survived… (full text at CIViC) PMID 27032107 · De Grève et al., 2016 · Open in CIViC | civic |
| EGFR Overexpression7 | ||||||||
| (prognostic) | Head and Neck Squamous Cell Carcinoma | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID782Primary tumors of 91 patients with head and neck squamous cell carcinoma were analyzed for expression of EGFR and TGF-alpha using IHC. Expression of EGFR or TGF-alpha were associated with reduced dise… (full text at CIViC) PMID 9625170 · Rubin Grandis et al., 1998 · Open in CIViC | civic |
| 〃 | Esophageal Squamous Cell CarcinomaALIAS | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID78455 tumor samples were analyzed for EGFR expression using IHC. PFS and OS was shorter for the EGFR high expressing group (18 pts) than for the low to moderate expression group (37 pts). PFS: 5.8 ± 0.5 … (full text at CIViC) PMID 26459251 · Jia et al., 2016 · Open in CIViC | civic |
| Unspecified therapy | Esophageal Squamous Cell CarcinomaALIAS | |||||||
| EGFR Overexpression + KRAS MutationEGFRKRAS3 | ||||||||
| Cetuximab | Colorectal Adenocarcinoma | Predictive | B | Supports Adverse Response | 3 | submitted | EID11059The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC | civic |
| (prognostic) | Colorectal Adenocarcinoma | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID11058The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC | civic |
| Cetuximab + ChemotherapyCombination | Colorectal Adenocarcinoma | |||||||
| EGFR P546S1 | ||||||||
| Cetuximab | Head and Neck Squamous Cell Carcinoma | Predictive | D | Supports Sensitivity Response | — | submitted | EID4672bp] In an in vitro study, a NIH3T3 cell line expressing EGFR P546S mutation demonstrated increased sensitivity to cetuximab treatment compared to NIH-3T3 cells expressing EGFR wild-type. Sensitivity w… (full text at CIViC) PMID 23578570 · Bahassi et al., 2013 · Open in CIViC | civic |
| EGFR P753S1 | ||||||||
| Cetuximab + SirolimusCombination | Skin Squamous Cell Carcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID108972-year old male patient presents with SCC with a mutation profile consistent with UV exposure. Sequencing revealed a number of abnormalities including P753S mutation in EGFR. Patient began therapy wi… (full text at CIViC) PMID 24934779 · Ganesan et al., 2016 · Open in CIViC | civic |
| EGFR P772_V774insPHV1 | ||||||||
| Erlotinib | Lung Adenocarcinoma | Predictive | C | Does Not Support Sensitivity Response | 3 | accepted | EID4803A 57 year old male 10 packyear former smoker with lung adenocarcinoma with EGFR P772_V774insPHV mutation was given erlotinib as first line treatment, and had progressive disease as best response with … (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC | civic |
Data updated 24 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.
EID982Afatinib is an irreversible covalent inhibitor of EGFR (second generation). This Phase III clinical trial (LUX-Lung 6; NCT01121393) was performed in Asian patients with EGFR mutant advanced NSCLC. 364… (full text at CIViC) PMID 24439929 · Wu et al., 2014 · Open in CIViC |
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| 〃 | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID883In a phase 2 study of patients with lung adenocarcinoma (stage IIIb with pleural effusion or stage IV) and EGFR mutations, treated with afatinib were assessed by objective response. 129 patients were … (full text at CIViC) PMID 22452895 · Yang et al., 2012 · Open in CIViC | civic |
| Cetuximab | Lung Adenocarcinoma | Predictive | D | Does Not Support Sensitivity Response | 3 | accepted | EID4292In an in vitro study, Ba/F3 cell line expressing EGFR L858R did not show sensitivity to cetuximab treatment, while cells expressing EGFR-RAD51 fusion were sensitive. Sensitivity was determined by asse… (full text at CIViC) PMID 27102076 · Konduri et al., 2016 · Open in CIViC | civic |
| Erlotinib | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID4290In a prospective study of 46 Caucasian, advanced lung adenocarcinoma patients harboring EGFR mutations, first-line erlotinib treatment was assessed. Average PFS and OS for these 46 patients was 11 mon… (full text at CIViC) PMID 27032107 · De Grève et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID4291In an in vitro study, Ba/F3 cell line expressing EGFR L858R was associated with sensitivity to erlotinib treatment (IC50 26.9 ± 12.4nM). EGFR L858R was used as a positive control for comparing sensiti… (full text at CIViC) PMID 27102076 · Konduri et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Small Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID4293In an in vitro study using NCI-H3255 cells (EGFR L858R mutation), inhibition of EGFR phosphorylation was used as an assay to determine sensitivity to EGFR tyrosine kinase inhibitors. NCI-H3255 cells d… (full text at CIViC) PMID 24893891 · Cross et al., 2014 · Open in CIViC | civic |
| Gefitinib | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID2634In a phase 3 clinical trial of Korean, never-smoker, lung adenocarcinoma patients, a subset of patients with EGFR mutations (n=42) treated with gefitinib were associated with improved overall response… (full text at CIViC) PMID 22370314 · Han et al., 2012 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID6183In a Japanese Phase III clinical trial, noninferiority of Gefitinib as compared to Erlotinib was assessed in 561 postoperative recurrent or stage IIIb/VI patients who had undergone prior chemotherapy … (full text at CIViC) PMID 27022112 · Urata et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 1 | accepted | EID2624Mutational profiling was performed on EGFR exons 18-24 from a group of 10 retrospectively chosen patients who had shown partial response or clinical improvement in response to gefitinib. Of 7 tumors w… (full text at CIViC) PMID 15329413 · Pao et al., 2004 · Open in CIViC | civic |
| Icotinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID12548A 67 year old female with stage IIIA lung adenocarcinoma had right lobectomy followed by 4 cycles adjuvant chemotherapy with pemetrexed and cisplatin. Next generation sequencing found EGFR L858R mutat… (full text at CIViC) PMID 35004270 · Wang et al., 2021 · Open in CIViC | civic |
| Osimertinib | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 4 | submitted | EID8053A 62 year old patient with 4 pack-year smoking history with back and flank pain was found to have metastatic lung adenocarcinoma by CT and MRI. Targeted NGS sequencing discovered an EGFR L858R mutatio… (full text at CIViC) PMID 32193290 · Starrett et al., 2020 · Open in CIViC | civic |
In a Japanese phase III study, lung adenocarcinoma patients with one or more of any mutation in their EGFR gene were treated with either Erlotinib or Gefitinib EGFR tyrosine kinase inhibitors to demon… (full text at CIViC)
PMID 27022112 · Urata et al., 2016 · Open in CIViC
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| EGFR Tyrosine Kinase Inhibitor Therapy + MetforminCombination | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12074In this trial, 139 patients with lung adenocarcinomas harbouring EGFR activating mutations were randomly assigned to two groups to receive either EGFR-TKIs alone (n = 70) or a combination of TGFR-TKIs… (full text at CIViC) PMID 31486833 · Arrieta et al., 2019 · Open in CIViC | civic |
| Predictive |
| B |
| Does Not Support Sensitivity Response |
| 3 |
| rejected |
EID833Expression of EGFR in 55 samples of esophageal squamous cell carcinoma with IHC was not predictive of response to EGFR inhibitor nimotuzumab. EGFR overexpression was related to poor OS and PFS. PMID 26459251 · Jia et al., 2016 · Open in CIViC |
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| (prognostic) | Esophageal Squamous Cell CarcinomaALIAS | Prognostic | B | Supports Poor Outcome | 3 | rejected | EID834Overexpression of EGFR in 55 samples of esophageal squamous cell carcinoma as assesesed by IHC, was related to poor OS and PFS (PFS: 5.8 ± 0.5 vs. 11.0 ± 2.8 months, P = 0.007; OS: 9.7 ± 0.5 vs. 21.5… (full text at CIViC) PMID 26459251 · Jia et al., 2016 · Open in CIViC | civic |
| Cetuximab | Head and Neck Squamous Cell Carcinoma | Predictive | B | Does Not Support Sensitivity Response | 4 | accepted | EID692EGFR expression level was not predicitive of response to cetuximab-containing first line regimens in recurrent or metastatic head and neck squamous cell carcinoma and KRAS-wild type colorectal carcino… (full text at CIViC) PMID 23265711 · Licitra et al., 2013 · Open in CIViC | civic |
| Cetuximab + DocetaxelCombination | Head and Neck Squamous Cell Carcinoma | Predictive | B | Does Not Support Sensitivity Response | 3 | accepted | EID84947 HNSCC patients treated with cetuximab/docetaxel were retrospectively analyzed for EGFRvIII, EGFR and AREG expression with IHC. 73 % of cases expressed high level of EGFR. EGFR expression had no imp… (full text at CIViC) PMID 21653686 · Tinhofer et al., 2011 · Open in CIViC | civic |
| Nimotuzumab | Esophageal Squamous Cell CarcinomaALIAS | Predictive | B | Does Not Support Sensitivity Response | 3 | accepted | EID78355 tumor samples were analyzed for EGFR expression using IHC. The objective response rate to anti-EGFR antibody nimotuzumab did not differ significantly between EGFR high- (18 pts) and EGFR low to mod… (full text at CIViC) PMID 26459251 · Jia et al., 2016 · Open in CIViC | civic |
| Predictive |
| B |
| Does Not Support Sensitivity Response |
| 3 |
| submitted |
EID11062The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC |
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