KRAS Mutation

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Chronic Myelomonocytic Leukemia1
KRAS Mutation	(predisposing)	Predisposing	D	Supports Likely Pathogenic	3	submitted	EID7166 Plays a causative role in leukemogenesis. RAS existed in a GTP-bound state in greater abundance than wild type, leading to increased phosphorylation of ERK (Fig. 2) Identified as oncogenic alleles in … (full text at CIViC) PMID 19075190 · Tyner et al., 2009 · Open in CIViC	civic
Colorectal Adenocarcinoma5
EGFR Overexpression AND KRAS Mutation	Cetuximab	Predictive	B	Supports Adverse Response	3	submitted	EID11059 The 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)

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Chronic Myelomonocytic Leukemia1

KRAS Mutation

(predisposing)

Predisposing

Supports Likely Pathogenic

submitted

EID7166

Plays a causative role in leukemogenesis. RAS existed in a GTP-bound state in greater abundance than wild type, leading to increased phosphorylation of ERK (Fig. 2) Identified as oncogenic alleles in … (full text at CIViC)

PMID 19075190 · Tyner et al., 2009 · Open in CIViC

civic

Colorectal Adenocarcinoma5

EGFR Overexpression AND KRAS Mutation

Cetuximab

Predictive

Supports Adverse Response

submitted

EID11059

The 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)

Diffuse Large B-Cell Lymphoma1
KRAS Mutation	(oncogenic)	Oncogenic	E	Supports Oncogenicity	4	submitted	EID11960 This study performed exome sequencing on 55 DLBCL tumor samples and identified several significantly mutated genes including KRAS. PMID 22343534 · Lohr et al., 2012 · Open in CIViC	civic

Diffuse Large B-Cell Lymphoma1

KRAS Mutation

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID11960

This study performed exome sequencing on 55 DLBCL tumor samples and identified several significantly mutated genes including KRAS.

PMID 22343534 · Lohr et al., 2012 · Open in CIViC

civic

Erdheim-Chester Disease1
NRAS Mutation OR KRAS Mutation OR RAF1 Mutation OR MAP2K1 Mutation OR MAP2K2 Mutation	Cobimetinib	Predictive	B	Supports Sensitivity Response	4	submitted	EID11328 In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. The overall response rate was 89% (90% CI: 73 - 100). Responses were durable, with no acquired … (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC	civic

Erdheim-Chester Disease1

NRAS Mutation OR KRAS Mutation OR RAF1 Mutation OR MAP2K1 Mutation OR MAP2K2 Mutation

Cobimetinib

Predictive

Supports Sensitivity Response

submitted

EID11328

In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. The overall response rate was 89% (90% CI: 73 - 100). Responses were durable, with no acquired … (full text at CIViC)

PMID 30867592 · Diamond et al., 2019 · Open in CIViC

civic

Hepatocellular Carcinoma1
KRAS Mutation	Refametinib + SorafenibCombination	Predictive	B	Supports Sensitivity Response	2	accepted	EID1642 Phase 2 study in Asian patients with unresectable hepatocellular carcinoma. 70 patients received refametinib (BAY 86-9766) plus sorafenib as study treatment. A retrospective biomarker analysis was per… (full text at CIViC) PMID 25294897 · Lim et al., 2014 · Open in CIViC	civic

Hepatocellular Carcinoma1

KRAS Mutation

Refametinib + SorafenibCombination

Predictive

Supports Sensitivity Response

accepted

EID1642

Phase 2 study in Asian patients with unresectable hepatocellular carcinoma. 70 patients received refametinib (BAY 86-9766) plus sorafenib as study treatment. A retrospective biomarker analysis was per… (full text at CIViC)

PMID 25294897 · Lim et al., 2014 · Open in CIViC

civic

Langerhans Cell Histiocytosis1
NRAS Mutation OR KRAS Mutation OR RAF1 Mutation OR MAP2K1 Mutation OR MAP2K2 Mutation	Cobimetinib	Predictive	B	Supports Sensitivity Response	4	submitted	EID11329 In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. Patients received cobimetinib at a starting dose of 60 mg daily for 21 days of each 28-day cycl… (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC	civic

Langerhans Cell Histiocytosis1

NRAS Mutation OR KRAS Mutation OR RAF1 Mutation OR MAP2K1 Mutation OR MAP2K2 Mutation

Cobimetinib

Predictive

Supports Sensitivity Response

submitted

EID11329

In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. Patients received cobimetinib at a starting dose of 60 mg daily for 21 days of each 28-day cycl… (full text at CIViC)

PMID 30867592 · Diamond et al., 2019 · Open in CIViC

civic

Lung Adenocarcinoma2
KRAS Mutation	(prognostic)	Prognostic	B	Supports Poor Outcome	4	accepted	EID1700 In a study of 1036 patients with lung adenocarcinoma, patients with KRAS mutations (n=241) showed worse prognosis (OS: 19 months versus 23 months; HR=1.21; P=0.048). PMID 22810899 · Johnson et al., 2013 · Open in CIViC	civic
KRAS Mutation	Salirasib	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID1218 In a study of 30 lung adenocarcinoma patients with documented KRAS mutations, farnesylthiosalicylic acid (Salirasib) mono-therapy resulted in no partial responses and did not improve overall survival … (full text at CIViC) PMID 21847063 · Riely et al., 2011 · Open in CIViC	civic

Lung Adenocarcinoma2

KRAS Mutation

(prognostic)

Prognostic

Supports Poor Outcome

accepted

EID1700

In a study of 1036 patients with lung adenocarcinoma, patients with KRAS mutations (n=241) showed worse prognosis (OS: 19 months versus 23 months; HR=1.21; P=0.048).

PMID 22810899 · Johnson et al., 2013 · Open in CIViC

civic

KRAS Mutation

Salirasib

Predictive

Does Not Support Sensitivity Response

accepted

EID1218

In a study of 30 lung adenocarcinoma patients with documented KRAS mutations, farnesylthiosalicylic acid (Salirasib) mono-therapy resulted in no partial responses and did not improve overall survival … (full text at CIViC)

PMID 21847063 · Riely et al., 2011 · Open in CIViC

civic

Lung Non-Small Cell Carcinoma20
KRAS Mutation	(prognostic)	Prognostic	B	Supports Poor Outcome	3	accepted	EID3715 Analysis 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
KRAS Mutation	Abemaciclib	Predictive	B	Supports Sensitivity Response	3	accepted	EID4842 In this multicenter phase I study of abemaciclib, a total of 225 patients were enrolled: 33 in dose escalation and 192 in tumor-specific cohorts. Radiographic responses were achieved in previously tre… (full text at CIViC) PMID 27217383 · Patnaik et al., 2016 · Open in CIViC	civic
KRAS Mutation	Afatinib + TrametinibCombination	Predictive	D	Supports Sensitivity Response	2	accepted	EID992 An shDNA screen identified synergy between ERBB3 Inhibition and MEK Inhibition in KRAS mutated cell lines. Dual EGFR/ERBB2 Inhibitors afatinib and dacomitinib and MEK Inhibition was synergistic in col… (full text at CIViC) PMID 24685132 · Sun et al., 2014 · Open in CIViC	civic
KRAS Mutation	B-Raf/VEGFR-2 Inhibitor RAF265 + SelumetinibCombination	Predictive	D	Supports Sensitivity Response	2	accepted	EID989 SiRNA Screening in 37 KRAS Mutant colorectal cancer cell lines identified RAF1 and MEK Inhibition as synergistic, whereas MEK Inhibition alone led to quick resistance via upregulation of RAF-signallin… (full text at CIViC) PMID 25199829 · Lamba et al., 2014 · Open in CIViC	civic
KRAS Mutation	Docetaxel	Predictive	B	Does Not Support Sensitivity Response	4	accepted	EID4997 Of the 275 patients assessable for KRAS mutation status, 49 (18%) were positive for KRAS mutation. There were no differences between treatments in OS, PFS, or response rates according to KRAS mutation… (full text at CIViC) PMID 20038723 · Douillard et al., 2010 · Open in CIViC	civic
KRAS Mutation	Docetaxel + ErlotinibSubstitutes	Predictive	B	Does Not Support Sensitivity Response	4	accepted	EID4996 222 EGFR-wt patients with advanced NSCLC were randomized to receive docetaxel or erlotinib In this study (4 patients not eligible, leaving 109 in each arm). KRAS was mutated in 25 and 26 out of 109 pa… (full text at CIViC) PMID 26209642 · Rulli et al., 2015 · Open in CIViC	civic
KRAS Mutation	Docetaxel + SelumetinibCombination	Predictive	A	Supports Resistance	5	accepted	EID2998 A phase 3 study of selumetinib and docetaxel in KRAS mutant, previously treated NSCLC. 866 were enrolled and 510 randomized. Median progression-free survival was 3.9 months with selumetinib + docetaxe… (full text at CIViC) PMID 28492898 · Jänne et al., 2017 · Open in CIViC	civic
KRAS Mutation	Docetaxel + SelumetinibCombination	Predictive	B	Supports Sensitivity Response	4	accepted	EID999 87 patients with KRAS mutant stage IIB-IV NSCLC after first line therapy were randomly assigned (1:1) to oral selumetunib and docetaxel or docetaxel and Placebo. Median OS was 9·4 months (6·8-13·6) in… (full text at CIViC) PMID 23200175 · Jänne et al., 2013 · Open in CIViC	civic
KRAS Mutation	Erlotinib	Predictive	B	Supports Resistance	2	accepted	EID2242 In advanced-stage (IIIB or IV) non-small cell lung cancer patients treated with erlotinib and placebo, patients whose tumors harbored KRAS mutations (n=8) had a lower 12-week progression-free survival… (full text at CIViC) PMID 22025157 · Ramalingam et al., 2011 · Open in CIViC	civic
KRAS Mutation	Erlotinib	Predictive	B	Supports Resistance	3	accepted	EID3895 In the placebo-controlled Phase III study SATURN, using erlotinib maintenance therapy for patients with advanced NSCLC who were selected for response or stable disease after first line chemotherapy, K… (full text at CIViC) PMID 21969500 · Brugger et al., 2011 · Open in CIViC	civic
KRAS Mutation	Erlotinib + SelumetinibCombination	Predictive	B	Does Not Support Sensitivity Response	4	accepted	EID4868 38 KRAS wild-type patients were randomized to erlotinib or combination of selumetinib with erlotinib. 41 KRAS mutant patients were randomized to selumetinib or the combination. The primary end points … (full text at CIViC) PMID 26802155 · Carter et al., 2016 · Open in CIViC	civic
KRAS Mutation	Erlotinib + TeprotumumabCombination	Predictive	B	Supports Sensitivity Response	2	accepted	EID3713 In advanced-stage (IIIB or IV) non-small cell lung cancer patients treated with erlotinib daily and teprotumumab (R1507) weekly or every three weeks, patients whose tumors harbored KRAS mutations had … (full text at CIViC) PMID 22025157 · Ramalingam et al., 2011 · Open in CIViC	civic
KRAS Mutation	Erlotinib + GefitinibSubstitutes	Predictive	B	Supports Resistance	3	accepted	EID2385 In a retrospective study, 166 non-small cell lung cancer (NSCLC) patients that tended to have selected characteristics known to be predictive for TKI sensitivity (i.e. women, never smokers, and patien… (full text at CIViC) PMID 21258250 · Ludovini et al., 2011 · Open in CIViC	civic
KRAS Mutation	Immune Checkpoint Inhibitor	Predictive	E	Supports Sensitivity Response	2	accepted	EID4864 This meta-analysis of 5 studies with 752 non-small cell lung cancer patients examined the association between PD-L1 expression and KRAS mutation status. KRAS-mutant tumors were marginally more likely … (full text at CIViC) PMID 28259530 · Li et al., 2017 · Open in CIViC	civic
KRAS Mutation	MEK Inhibitor RO4987655	Predictive	B	Does Not Support Resistance	3	accepted	EID997 This was a phase I expansion and pharmacodynamic study of oral MEK inhibitor RO4987655 on advanced cancer. Of 18 patients with KRAS mutant non-small cell lung cancer (NSCLC), 10 experienced clinical b… (full text at CIViC) PMID 24947927 · Zimmer et al., 2014 · Open in CIViC	civic
KRAS Mutation	Atezolizumab + NivolumabSubstitutes	Predictive	B	Supports Sensitivity Response	3	accepted	EID4863 A meta-analysis of randomized trials to investigate if KRAS mutation status affects survival benefits of immune checkpoint inhibition (ICI) in patients with advanced NSCLC. Of 3 eligible studies using… (full text at CIViC) PMID 28525386 · Kim et al., 2017 · Open in CIViC	civic
KRAS Mutation	Pembrolizumab	Predictive	D	Supports Sensitivity Response	3	submitted	EID4865 In this study we investigated the correlation between PD-L1 expression and KRAS mutation and the functional significance of PD-1/PD-L1 blockade in KRAS-mutant lung adenocarcinoma. We found that PD-L1 … (full text at CIViC) PMID 28451792 · Chen et al., 2017 · Open in CIViC	civic
KRAS Mutation	Trametinib	Predictive	B	Supports Sensitivity Response	2	accepted	EID1220 In a phase 1 clinical trial for the use of trametinib for various advanced solid tumors, 22 out of 30 NSCLC patients harbored KRAS mutations. Of those 22 patients with mutant KRAS, 8 saw reductions in… (full text at CIViC) PMID 22805291 · Infante et al., 2012 · Open in CIViC	civic
KRAS Mutation	Trametinib	Predictive	B	Does Not Support Sensitivity Response	4	accepted	EID4867 In this phase II trial, trametinib or docetaxel was given to patients with advanced KRAS-mutant NSCLC. Median PFS was 12 weeks in the trametinib arm and 11 weeks in the docetaxel arm (HR 1.14; p = 0.5… (full text at CIViC) PMID 25722381 · Blumenschein et al., 2015 · Open in CIViC	civic
KRAS Mutation	Docetaxel + Pemetrexed + TrametinibCombination	Predictive	B	Supports Sensitivity Response	3	accepted	EID4862 This phase I/Ib two-part study evaluated trametinib in combination with anticancer agents docetaxel or pemetrexed in NSCLC with and without KRAS mutations. Confirmed partial response (PR) was observed… (full text at CIViC) PMID 27876675 · Gandara et al., 2017 · Open in CIViC	civic

Lung Non-Small Cell Carcinoma20

KRAS Mutation

(prognostic)

Prognostic

Supports Poor Outcome

accepted

EID3715

Analysis 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

KRAS Mutation

Abemaciclib

Predictive

Supports Sensitivity Response

accepted

EID4842

In this multicenter phase I study of abemaciclib, a total of 225 patients were enrolled: 33 in dose escalation and 192 in tumor-specific cohorts. Radiographic responses were achieved in previously tre… (full text at CIViC)

PMID 27217383 · Patnaik et al., 2016 · Open in CIViC

civic

KRAS Mutation

Afatinib + TrametinibCombination

Predictive

Supports Sensitivity Response

accepted

EID992

An shDNA screen identified synergy between ERBB3 Inhibition and MEK Inhibition in KRAS mutated cell lines. Dual EGFR/ERBB2 Inhibitors afatinib and dacomitinib and MEK Inhibition was synergistic in col… (full text at CIViC)

PMID 24685132 · Sun et al., 2014 · Open in CIViC

civic

KRAS Mutation

B-Raf/VEGFR-2 Inhibitor RAF265 + SelumetinibCombination

Predictive

Supports Sensitivity Response

accepted

EID989

SiRNA Screening in 37 KRAS Mutant colorectal cancer cell lines identified RAF1 and MEK Inhibition as synergistic, whereas MEK Inhibition alone led to quick resistance via upregulation of RAF-signallin… (full text at CIViC)

PMID 25199829 · Lamba et al., 2014 · Open in CIViC

civic

KRAS Mutation

Docetaxel

Predictive

Does Not Support Sensitivity Response

accepted

EID4997

Of the 275 patients assessable for KRAS mutation status, 49 (18%) were positive for KRAS mutation. There were no differences between treatments in OS, PFS, or response rates according to KRAS mutation… (full text at CIViC)

PMID 20038723 · Douillard et al., 2010 · Open in CIViC

civic

KRAS Mutation

Docetaxel + ErlotinibSubstitutes

Predictive

Does Not Support Sensitivity Response

accepted

EID4996

222 EGFR-wt patients with advanced NSCLC were randomized to receive docetaxel or erlotinib In this study (4 patients not eligible, leaving 109 in each arm). KRAS was mutated in 25 and 26 out of 109 pa… (full text at CIViC)

PMID 26209642 · Rulli et al., 2015 · Open in CIViC

civic

KRAS Mutation

Docetaxel + SelumetinibCombination

Predictive

Supports Resistance

accepted

EID2998

A phase 3 study of selumetinib and docetaxel in KRAS mutant, previously treated NSCLC. 866 were enrolled and 510 randomized. Median progression-free survival was 3.9 months with selumetinib + docetaxe… (full text at CIViC)

PMID 28492898 · Jänne et al., 2017 · Open in CIViC

civic

KRAS Mutation

Docetaxel + SelumetinibCombination

Predictive

Supports Sensitivity Response

accepted

EID999

87 patients with KRAS mutant stage IIB-IV NSCLC after first line therapy were randomly assigned (1:1) to oral selumetunib and docetaxel or docetaxel and Placebo. Median OS was 9·4 months (6·8-13·6) in… (full text at CIViC)

PMID 23200175 · Jänne et al., 2013 · Open in CIViC

civic

KRAS Mutation

Erlotinib

Predictive

Supports Resistance

accepted

EID2242

In advanced-stage (IIIB or IV) non-small cell lung cancer patients treated with erlotinib and placebo, patients whose tumors harbored KRAS mutations (n=8) had a lower 12-week progression-free survival… (full text at CIViC)

PMID 22025157 · Ramalingam et al., 2011 · Open in CIViC

civic

KRAS Mutation

Erlotinib

Predictive

Supports Resistance

accepted

EID3895

In the placebo-controlled Phase III study SATURN, using erlotinib maintenance therapy for patients with advanced NSCLC who were selected for response or stable disease after first line chemotherapy, K… (full text at CIViC)

PMID 21969500 · Brugger et al., 2011 · Open in CIViC

civic

KRAS Mutation

Erlotinib + SelumetinibCombination

Predictive

Does Not Support Sensitivity Response

accepted

EID4868

38 KRAS wild-type patients were randomized to erlotinib or combination of selumetinib with erlotinib. 41 KRAS mutant patients were randomized to selumetinib or the combination. The primary end points … (full text at CIViC)

PMID 26802155 · Carter et al., 2016 · Open in CIViC

civic

KRAS Mutation

Erlotinib + TeprotumumabCombination

Predictive

Supports Sensitivity Response

accepted

EID3713

In advanced-stage (IIIB or IV) non-small cell lung cancer patients treated with erlotinib daily and teprotumumab (R1507) weekly or every three weeks, patients whose tumors harbored KRAS mutations had … (full text at CIViC)

PMID 22025157 · Ramalingam et al., 2011 · Open in CIViC

civic

KRAS Mutation

Erlotinib + GefitinibSubstitutes

Predictive

Supports Resistance

accepted

EID2385

In a retrospective study, 166 non-small cell lung cancer (NSCLC) patients that tended to have selected characteristics known to be predictive for TKI sensitivity (i.e. women, never smokers, and patien… (full text at CIViC)

PMID 21258250 · Ludovini et al., 2011 · Open in CIViC

civic

KRAS Mutation

Immune Checkpoint Inhibitor

Predictive

Supports Sensitivity Response

accepted

EID4864

This meta-analysis of 5 studies with 752 non-small cell lung cancer patients examined the association between PD-L1 expression and KRAS mutation status. KRAS-mutant tumors were marginally more likely … (full text at CIViC)

PMID 28259530 · Li et al., 2017 · Open in CIViC

civic

KRAS Mutation

MEK Inhibitor RO4987655

Predictive

Does Not Support Resistance

accepted

EID997

This was a phase I expansion and pharmacodynamic study of oral MEK inhibitor RO4987655 on advanced cancer. Of 18 patients with KRAS mutant non-small cell lung cancer (NSCLC), 10 experienced clinical b… (full text at CIViC)

PMID 24947927 · Zimmer et al., 2014 · Open in CIViC

civic

KRAS Mutation

Atezolizumab + NivolumabSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID4863

A meta-analysis of randomized trials to investigate if KRAS mutation status affects survival benefits of immune checkpoint inhibition (ICI) in patients with advanced NSCLC. Of 3 eligible studies using… (full text at CIViC)

PMID 28525386 · Kim et al., 2017 · Open in CIViC

civic

KRAS Mutation

Pembrolizumab

Predictive

Supports Sensitivity Response

submitted

EID4865

In this study we investigated the correlation between PD-L1 expression and KRAS mutation and the functional significance of PD-1/PD-L1 blockade in KRAS-mutant lung adenocarcinoma. We found that PD-L1 … (full text at CIViC)

PMID 28451792 · Chen et al., 2017 · Open in CIViC

civic

KRAS Mutation

Trametinib

Predictive

Supports Sensitivity Response

accepted

EID1220

In a phase 1 clinical trial for the use of trametinib for various advanced solid tumors, 22 out of 30 NSCLC patients harbored KRAS mutations. Of those 22 patients with mutant KRAS, 8 saw reductions in… (full text at CIViC)

PMID 22805291 · Infante et al., 2012 · Open in CIViC

civic

KRAS Mutation

Trametinib

Predictive

Does Not Support Sensitivity Response

accepted

EID4867

In this phase II trial, trametinib or docetaxel was given to patients with advanced KRAS-mutant NSCLC. Median PFS was 12 weeks in the trametinib arm and 11 weeks in the docetaxel arm (HR 1.14; p = 0.5… (full text at CIViC)

PMID 25722381 · Blumenschein et al., 2015 · Open in CIViC

civic

KRAS Mutation

Docetaxel + Pemetrexed + TrametinibCombination

Predictive

Supports Sensitivity Response

accepted

EID4862

This phase I/Ib two-part study evaluated trametinib in combination with anticancer agents docetaxel or pemetrexed in NSCLC with and without KRAS mutations. Confirmed partial response (PR) was observed… (full text at CIViC)

PMID 27876675 · Gandara et al., 2017 · Open in CIViC

civic

Malignant Colorectal Neoplasm18
KRAS Mutation	Bevacizumab + ChemotherapyCombination	Predictive	B	Supports Resistance	4	accepted	EID1139 Meta-Analysis of 12 studies with 2,266 patients (54 % were KRAS wt). The pooled response rates (RR) for KRAS wild-type (wt) versus mutated (mut) patients were 54.8 and 48.3 %, respectively (OR 1.42, P… (full text at CIViC) PMID 23828442 · Petrelli et al., 2013 · Open in CIViC	civic
KRAS Mutation	Binimetinib + PalbociclibCombination	Predictive	D	Supports Sensitivity Response	4	accepted	EID4869 A preclinical study to investigate the efficacy of Binimetinib, Palbociclib and the combination on KRAS mutant colorectal cancer cell lines, cell line-derived and patient-derived xenografts. The com… (full text at CIViC) PMID 27167191 · Lee et al., 2016 · Open in CIViC	civic
KRAS Mutation	B-Raf/VEGFR-2 Inhibitor RAF265 + SelumetinibCombination	Predictive	D	Supports Sensitivity Response	4	accepted	EID988 SiRNA Screening in 37 KRAS Mutant colorectal cancer cell lines identified RAF1 and MEK Inhibition as synergistic, whereas MEK Inhibition alone led to quick resistance via upregulation of RAF-signallin… (full text at CIViC) PMID 25199829 · Lamba et al., 2014 · Open in CIViC	civic
KRAS Mutation	Cetuximab	Predictive	B	Supports Resistance	3	submitted	EID6464 This study shows that KRAS mutations such as G12D, G13D and KRAS amplification are frequent drivers of acquired resistance to cetuximab in colorectal cancers. KRAS mutant clones can be detected throug… (full text at CIViC) PMID 22722830 · Misale et al., 2012 · Open in CIViC	civic
KRAS Mutation	Cetuximab	Predictive	D	Supports Resistance	3	accepted	EID1702 A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xeno… (full text at CIViC) PMID 22586653 · Bertotti et al., 2011 · Open in CIViC	civic
KRAS Mutation	Cetuximab + ChemotherapyCombination	Predictive	B	Supports Resistance	4	accepted	EID3704 This was a retrospective study of 605 patients with metastatic, chemotherapy refractory colorectal cancer treated with cetuximab + chemotherapy. Patients with KRAS mutant tumors (total [n = 253], codo… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
KRAS Mutation	Cetuximab + DasatinibCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID947 Combined treatment with dasatinib and cetuximab, but not either agent in monotherapy, had an antitumor efficacy in-vitro and in xenografts. These results were based on three KRAS mutant cell lines (LS… (full text at CIViC) PMID 20956938 · Dunn et al., 2011 · Open in CIViC	civic
KRAS Mutation	Cetuximab + PanitumumabSubstitutes	Predictive	A	Supports Resistance	5	accepted	EID5345 NCCN guidelines indicate colorectal cancer patients with KRAS mutations should not be treated with the anti-EGFR therapies cetuximab or panitumumab. PMID 28275037 · Benson et al., 2017 · Open in CIViC	civic
KRAS Mutation	Cetuximab + SelumetinibCombination	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID4866 A phase I study to determine the tolerability and pharmacokinetics of Selumetinib and Cetuximab with an expanded cohort in KRAS-mutant CRC. In the KRAS-mutant CRC dose expansion cohort 14 patients we… (full text at CIViC) PMID 26666244 · Deming et al., 2016 · Open in CIViC	civic
KRAS Mutation	Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor + Immunomodulatory OligonucleotideCombination	Predictive	D	Supports Sensitivity Response	2	accepted	EID943 TLR9 agonist immunomodulatory oligonucleotide (IMO) led to inhibited survival of LS174T colorectal cancer and AsPC1 pancreatic cancer cell lines with KRAS mutations. PMID 21890455 · Rosa et al., 2011 · Open in CIViC	civic
KRAS Mutation	Ixazomib	Predictive	D	Supports Resistance	1	accepted	EID1182 Preclinical study in colorectal cancer xenografts. KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cell line. KRAS wild-type, but not KRAS mutant tumors were sensitive to proteasome… (full text at CIViC) PMID 26709701 · Chattopadhyay et al., 2015 · Open in CIViC	civic
KRAS Mutation	MEK Inhibitor RO4987655	Predictive	B	Does Not Support Sensitivity Response	2	accepted	EID998 Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655). All 25 patients with KRAS mutant colorectal cancer experienced PD. Median days on treatment was 57 (5-269).… (full text at CIViC) PMID 24947927 · Zimmer et al., 2014 · Open in CIViC	civic
KRAS Mutation	Metformin	Predictive	B	Supports Sensitivity Response	4	submitted	EID8301 A retrospective study of 2335 metastatic colorectal cancer (mCRC) patients, including 282 patients with type 2 diabetes mellitus (T2DM), examined the survival effects of metformin use in mCRC. Diabeti… (full text at CIViC) PMID 32444490 · Xie et al., 2020 · Open in CIViC	civic
KRAS Mutation	Refametinib	Predictive	C	Does Not Support Sensitivity Response	2	accepted	EID1001 Phase I trial of the mitogen-activated protein kinase 1/2 inhibitor BAY 86-9766. 4 patients with KRAS +/- PIK3CA mutant colorectal cancer. 3 with SD, 1 with PD. PMID 23434733 · Weekes et al., 2013 · Open in CIViC	civic
KRAS Mutation	Selumetinib + TeprotumumabCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID1004 Preclinial data from KRAS mutant colorectal cancer cell lines show syngergistic effect on cell viability and apoptosis in vitro and in vivo when MEK and IGF-IR are inhibited concomitantly. In other ce… (full text at CIViC) PMID 21985784 · Ebi et al., 2011 · Open in CIViC	civic
KRAS Mutation	Afatinib + TrametinibCombination	Predictive	D	Supports Sensitivity Response	4	accepted	EID991 An shDNA Screen identified synergy betwenn ERBB3 Inhibition and MEK Inhibition in KRAS mutated cell lines. Dual EGFR/ERBB2 Inhibitors afatinib and dacomitinib and MEK Inhibition was synergistic in col… (full text at CIViC) PMID 24685132 · Sun et al., 2014 · Open in CIViC	civic
MET Amplification AND NOT KRAS Mutation	Cetuximab + CrizotinibCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID1979 Functional studies show that MET activation confers resistance to anti-EGFR therapy both in vitro and in vivo. Notably, in patient-derived colorectal cancer xenografts, MET amplification correlated wi… (full text at CIViC) PMID 23729478 · Bardelli et al., 2013 · Open in CIViC	civic
MET Amplification AND NOT KRAS Mutation	Cetuximab/Irinotecan Regimen + PanitumumabSubstitutes	Predictive	C	Supports Resistance	3	accepted	EID1971 7 patients with acquired resistance to EGFR inhibitors were analyzed in this study. Of these, 4 did not develop KRAS mutations. Post- and Pre-Treatment tissued was available of three patients and MET … (full text at CIViC) PMID 23729478 · Bardelli et al., 2013 · Open in CIViC	civic

Malignant Colorectal Neoplasm18

KRAS Mutation

Bevacizumab + ChemotherapyCombination

Predictive

Supports Resistance

accepted

EID1139

Meta-Analysis of 12 studies with 2,266 patients (54 % were KRAS wt). The pooled response rates (RR) for KRAS wild-type (wt) versus mutated (mut) patients were 54.8 and 48.3 %, respectively (OR 1.42, P… (full text at CIViC)

PMID 23828442 · Petrelli et al., 2013 · Open in CIViC

civic

KRAS Mutation

Binimetinib + PalbociclibCombination

Predictive

Supports Sensitivity Response

accepted

EID4869

A preclinical study to investigate the efficacy of Binimetinib, Palbociclib and the combination on KRAS mutant colorectal cancer cell lines, cell line-derived and patient-derived xenografts. The com… (full text at CIViC)

PMID 27167191 · Lee et al., 2016 · Open in CIViC

civic

KRAS Mutation

B-Raf/VEGFR-2 Inhibitor RAF265 + SelumetinibCombination

Predictive

Supports Sensitivity Response

accepted

EID988

PMID 25199829 · Lamba et al., 2014 · Open in CIViC

civic

KRAS Mutation

Cetuximab

Predictive

Supports Resistance

submitted

EID6464

This study shows that KRAS mutations such as G12D, G13D and KRAS amplification are frequent drivers of acquired resistance to cetuximab in colorectal cancers. KRAS mutant clones can be detected throug… (full text at CIViC)

PMID 22722830 · Misale et al., 2012 · Open in CIViC

civic

KRAS Mutation

Cetuximab

Predictive

Supports Resistance

accepted

EID1702

A cohort of patient-derived xenografts (PDX) from 85 patients with metastatic colorectal cancer was created. PDX were treated with cetuximab and mechanisms of resistance investigated. None of the xeno… (full text at CIViC)

PMID 22586653 · Bertotti et al., 2011 · Open in CIViC

civic

KRAS Mutation

Cetuximab + ChemotherapyCombination

Predictive

Supports Resistance

accepted

EID3704

This was a retrospective study of 605 patients with metastatic, chemotherapy refractory colorectal cancer treated with cetuximab + chemotherapy. Patients with KRAS mutant tumors (total [n = 253], codo… (full text at CIViC)

PMID 20619739 · De Roock et al., 2010 · Open in CIViC

civic

KRAS Mutation

Cetuximab + DasatinibCombination

Predictive

Supports Sensitivity Response

accepted

EID947

Combined treatment with dasatinib and cetuximab, but not either agent in monotherapy, had an antitumor efficacy in-vitro and in xenografts. These results were based on three KRAS mutant cell lines (LS… (full text at CIViC)

PMID 20956938 · Dunn et al., 2011 · Open in CIViC

civic

KRAS Mutation

Cetuximab + PanitumumabSubstitutes

Predictive

Supports Resistance

accepted

EID5345

NCCN guidelines indicate colorectal cancer patients with KRAS mutations should not be treated with the anti-EGFR therapies cetuximab or panitumumab.

PMID 28275037 · Benson et al., 2017 · Open in CIViC

civic

KRAS Mutation

Cetuximab + SelumetinibCombination

Predictive

Does Not Support Sensitivity Response

accepted

EID4866

A phase I study to determine the tolerability and pharmacokinetics of Selumetinib and Cetuximab with an expanded cohort in KRAS-mutant CRC. In the KRAS-mutant CRC dose expansion cohort 14 patients we… (full text at CIViC)

PMID 26666244 · Deming et al., 2016 · Open in CIViC

civic

KRAS Mutation

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor + Immunomodulatory OligonucleotideCombination

Predictive

Supports Sensitivity Response

accepted

EID943

TLR9 agonist immunomodulatory oligonucleotide (IMO) led to inhibited survival of LS174T colorectal cancer and AsPC1 pancreatic cancer cell lines with KRAS mutations.

PMID 21890455 · Rosa et al., 2011 · Open in CIViC

civic

KRAS Mutation

Ixazomib

Predictive

Supports Resistance

accepted

EID1182

Preclinical study in colorectal cancer xenografts. KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cell line. KRAS wild-type, but not KRAS mutant tumors were sensitive to proteasome… (full text at CIViC)

PMID 26709701 · Chattopadhyay et al., 2015 · Open in CIViC

civic

KRAS Mutation

MEK Inhibitor RO4987655

Predictive

Does Not Support Sensitivity Response

accepted

EID998

Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655). All 25 patients with KRAS mutant colorectal cancer experienced PD. Median days on treatment was 57 (5-269).… (full text at CIViC)

PMID 24947927 · Zimmer et al., 2014 · Open in CIViC

civic

KRAS Mutation

Metformin

Predictive

Supports Sensitivity Response

submitted

EID8301

A retrospective study of 2335 metastatic colorectal cancer (mCRC) patients, including 282 patients with type 2 diabetes mellitus (T2DM), examined the survival effects of metformin use in mCRC. Diabeti… (full text at CIViC)

PMID 32444490 · Xie et al., 2020 · Open in CIViC

civic

KRAS Mutation

Refametinib

Predictive

Does Not Support Sensitivity Response

accepted

EID1001

Phase I trial of the mitogen-activated protein kinase 1/2 inhibitor BAY 86-9766. 4 patients with KRAS +/- PIK3CA mutant colorectal cancer. 3 with SD, 1 with PD.

PMID 23434733 · Weekes et al., 2013 · Open in CIViC

civic

KRAS Mutation

Selumetinib + TeprotumumabCombination

Predictive

Supports Sensitivity Response

accepted

EID1004

Preclinial data from KRAS mutant colorectal cancer cell lines show syngergistic effect on cell viability and apoptosis in vitro and in vivo when MEK and IGF-IR are inhibited concomitantly. In other ce… (full text at CIViC)

PMID 21985784 · Ebi et al., 2011 · Open in CIViC

civic

KRAS Mutation

Afatinib + TrametinibCombination

Predictive

Supports Sensitivity Response

accepted

EID991

An shDNA Screen identified synergy betwenn ERBB3 Inhibition and MEK Inhibition in KRAS mutated cell lines. Dual EGFR/ERBB2 Inhibitors afatinib and dacomitinib and MEK Inhibition was synergistic in col… (full text at CIViC)

PMID 24685132 · Sun et al., 2014 · Open in CIViC

civic

MET Amplification AND NOT KRAS Mutation

Cetuximab + CrizotinibCombination

Predictive

Supports Sensitivity Response

accepted

EID1979

Functional studies show that MET activation confers resistance to anti-EGFR therapy both in vitro and in vivo. Notably, in patient-derived colorectal cancer xenografts, MET amplification correlated wi… (full text at CIViC)

PMID 23729478 · Bardelli et al., 2013 · Open in CIViC

civic

MET Amplification AND NOT KRAS Mutation

Cetuximab/Irinotecan Regimen + PanitumumabSubstitutes

Predictive

Supports Resistance

accepted

EID1971

7 patients with acquired resistance to EGFR inhibitors were analyzed in this study. Of these, 4 did not develop KRAS mutations. Post- and Pre-Treatment tissued was available of three patients and MET … (full text at CIViC)

PMID 23729478 · Bardelli et al., 2013 · Open in CIViC

civic

Evidence by cancer (66 items)

Clinical significance (0)