KRAS G12R

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Lung Non-Small Cell Carcinoma2
KRAS G12R	Erlotinib	Predictive	C	Supports Resistance	—	submitted	EID3993 In a retrospective study of 274 stage IIIB or IV non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (25/55) treated with erlotinib plus chemotherapy were associated with decreas… (full text at CIViC) PMID 16043828 · Eberhard et al., 2005 · Open in CIViC	civic
KRAS G12R	Erlotinib	Predictive	C	Supports Resistance	—	submitted	EID3995 In a prospective study of 522 European non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (42/307) treated with erlotinib as a second-, third-line or more treatment were associa… (full text at CIViC) PMID 22982650 · Cadranel et al., 2012 · Open in CIViC	civic

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Lung Non-Small Cell Carcinoma2

KRAS G12R

Erlotinib

Predictive

Supports Resistance

—

submitted

EID3993

In a retrospective study of 274 stage IIIB or IV non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (25/55) treated with erlotinib plus chemotherapy were associated with decreas… (full text at CIViC)

PMID 16043828 · Eberhard et al., 2005 · Open in CIViC

civic

KRAS G12R

Erlotinib

Predictive

Supports Resistance

—

submitted

EID3995

In a prospective study of 522 European non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (42/307) treated with erlotinib as a second-, third-line or more treatment were associa… (full text at CIViC)

PMID 22982650 · Cadranel et al., 2012 · Open in CIViC

civic

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
12579	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts	2	Malignant tumor of urinary bladder; Squamous cell lung carcinoma; Non-small cell lung carcinoma; RASopathy; Neoplasm; Adenoid cystic carcinoma	germline/somatic	7	Jul 04, 2022	clinvar

Variation

Clinical significance

Review status

Stars

Conditions

Origin

Submitters

Last evaluated

Source

12579

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Malignant tumor of urinary bladder; Squamous cell lung carcinoma; Non-small cell lung carcinoma; RASopathy; Neoplasm; Adenoid cystic carcinoma

germline/somatic

Jul 04, 2022

clinvar

Malignant Colon Neoplasm1
KRAS G12R	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3998 In a phase 3 clinical study,�BRAF wild-type stage III colon cancer patients harboring KRAS G12R mutation (n=5) and treated with cetuximab plus standard chemotherapy were associated with decreased dise… (full text at CIViC) PMID 24687927 · Yoon et al., 2014 · Open in CIViC	civic

Malignant Colon Neoplasm1

KRAS G12R

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3998

In a phase 3 clinical study,�BRAF wild-type stage III colon cancer patients harboring KRAS G12R mutation (n=5) and treated with cetuximab plus standard chemotherapy were associated with decreased dise… (full text at CIViC)

PMID 24687927 · Yoon et al., 2014 · Open in CIViC

civic

Malignant Colorectal Neoplasm13
KRAS G12R	Cetuximab	Predictive	C	Supports Resistance	—	rejected	EID3984 In a retrospective study of 168 metastatic colorectal cancer patients, patients with a KRAS exon 2 mutation (32/92) treated with cetuximab as salvage therapy (second-line therapy or higher) in combina… (full text at CIViC) PMID 19603024 · Souglakos et al., 2009 · Open in CIViC	civic
KRAS G12R	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3985 In a retrospective study of 59 metastatic, chemotherapy-refractory, colorectal cancer patients, patients with a KRAS exon 2 mutation (n=22) treated with cetuximab and standard chemotherapy were assoc… (full text at CIViC) PMID 17375050 · Di Fiore et al., 2007 · Open in CIViC	civic
KRAS G12R	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3986 In a retrospective study of 89 metastatic irinotecan-refractory colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation (n=24) treated with cetuximab plus chemotherapy were associated… (full text at CIViC) PMID 18202412 · Lièvre et al., 2008 · Open in CIViC	civic
KRAS G12R	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3988 In a retrospective study of 572 advanced colorectal cancer patients, patients treated with cetuximab and best supportive care with a KRAS exon 2 mutation (81/164) were associated with reduced response… (full text at CIViC) PMID 18946061 · Karapetis et al., 2008 · Open in CIViC	civic
KRAS G12R	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3990 In a retrospective study of 95 metastatic colorectal cancer patients, patients harboring KRAS activating mutation (n=33) and treated with cetuximab plus standard chemotherapy were reportedly non-respo… (full text at CIViC) PMID 20010090 · Yen et al., 2010 · Open in CIViC	civic
KRAS G12R	Cetuximab	Predictive	D	Supports Resistance	4	accepted	EID3989 In an in vitro study to identify cetuximab-resistant clones following continuous drug treatment, a resistant clone of the Lim1215 colorectal cancer cell line was identified to have the KRAS G12R mutat… (full text at CIViC) PMID 22722830 · Misale et al., 2012 · Open in CIViC	civic
KRAS G12R	Cetuximab + ChemotherapyCombination	Predictive	C	Supports Resistance	3	accepted	EID3987 Three patients participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored KRAS G12R, were wildtype for NRAS, BRAF and PIK… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
KRAS G12R	Panitumumab	Predictive	C	Supports Resistance	—	accepted	EID2264 In a retrospective study of 427 metastatic colorectal patients, KRAS mutations were observed in 43% of the tumor samples. Patients with mutations in codon 12 or 13 of KRAS were associated with reduced… (full text at CIViC) PMID 18316791 · Amado et al., 2008 · Open in CIViC	civic
KRAS G12R	Panitumumab	Predictive	C	Supports Resistance	—	submitted	EID2265 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 16953233 · Oliveira et al., 2007 · Open in CIViC	civic
KRAS G12R	Panitumumab	Predictive	C	Supports Resistance	—	submitted	EID2266 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 2547513 · Bos, 1989 · Open in CIViC	civic
KRAS G12R	Panitumumab	Predictive	C	Supports Resistance	—	submitted	EID2267 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 8462792 · Benhattar et al., 1993 · Open in CIViC	civic
KRAS G12R	Regorafenib Anhydrous	Predictive	D	Supports Resistance	1	accepted	EID3991 In an in vitro study, a human colon adenocarcinoma SW48 cell line expressing KRAS G12R mutation demonstrated resistance to regorafenib treatment (IC50: 181.77 nM vs. 114.28 nM, P<0.01) compared to SW4… (full text at CIViC) PMID 26161928 · Camaj et al., 2015 · Open in CIViC	civic
KRAS G12R	Sunitinib	Predictive	D	Supports Resistance	—	submitted	EID3992 In an in vitro study, colorectal cancer SW48 cell line expressing KRAS G12R mutation demonstrated reduced sensitivity to sunitinib treatment (IC50: 4.5uM vs. 2.6uM, P<0.05) compared to SW48 cells expr… (full text at CIViC) PMID 23455880 · Modest et al., 2013 · Open in CIViC	civic

Malignant Colorectal Neoplasm13

KRAS G12R

Cetuximab

Predictive

Supports Resistance

—

rejected

EID3984

In a retrospective study of 168 metastatic colorectal cancer patients, patients with a KRAS exon 2 mutation (32/92) treated with cetuximab as salvage therapy (second-line therapy or higher) in combina… (full text at CIViC)

PMID 19603024 · Souglakos et al., 2009 · Open in CIViC

civic

KRAS G12R

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3985

In a retrospective study of 59 metastatic, chemotherapy-refractory, colorectal cancer patients, patients with a KRAS exon 2 mutation (n=22) treated with cetuximab and standard chemotherapy were assoc… (full text at CIViC)

PMID 17375050 · Di Fiore et al., 2007 · Open in CIViC

civic

KRAS G12R

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3986

In a retrospective study of 89 metastatic irinotecan-refractory colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation (n=24) treated with cetuximab plus chemotherapy were associated… (full text at CIViC)

PMID 18202412 · Lièvre et al., 2008 · Open in CIViC

civic

KRAS G12R

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3988

In a retrospective study of 572 advanced colorectal cancer patients, patients treated with cetuximab and best supportive care with a KRAS exon 2 mutation (81/164) were associated with reduced response… (full text at CIViC)

PMID 18946061 · Karapetis et al., 2008 · Open in CIViC

civic

KRAS G12R

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3990

In a retrospective study of 95 metastatic colorectal cancer patients, patients harboring KRAS activating mutation (n=33) and treated with cetuximab plus standard chemotherapy were reportedly non-respo… (full text at CIViC)

PMID 20010090 · Yen et al., 2010 · Open in CIViC

civic

KRAS G12R

Cetuximab

Predictive

Supports Resistance

accepted

EID3989

In an in vitro study to identify cetuximab-resistant clones following continuous drug treatment, a resistant clone of the Lim1215 colorectal cancer cell line was identified to have the KRAS G12R mutat… (full text at CIViC)

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

civic

KRAS G12R

Cetuximab + ChemotherapyCombination

Predictive

Supports Resistance

accepted

EID3987

Three patients participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored KRAS G12R, were wildtype for NRAS, BRAF and PIK… (full text at CIViC)

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

civic

KRAS G12R

Panitumumab

Predictive

Supports Resistance

—

accepted

EID2264

In a retrospective study of 427 metastatic colorectal patients, KRAS mutations were observed in 43% of the tumor samples. Patients with mutations in codon 12 or 13 of KRAS were associated with reduced… (full text at CIViC)

PMID 18316791 · Amado et al., 2008 · Open in CIViC

civic

KRAS G12R

Panitumumab

Predictive

Supports Resistance

—

submitted

EID2265

KRAS mutations have been reported in 30-50% of colorectal carcinomas.

PMID 16953233 · Oliveira et al., 2007 · Open in CIViC

civic

KRAS G12R

Panitumumab

Predictive

Supports Resistance

—

submitted

EID2266

KRAS mutations have been reported in 30-50% of colorectal carcinomas.

PMID 2547513 · Bos, 1989 · Open in CIViC

civic

KRAS G12R

Panitumumab

Predictive

Supports Resistance

—

submitted

EID2267

KRAS mutations have been reported in 30-50% of colorectal carcinomas.

PMID 8462792 · Benhattar et al., 1993 · Open in CIViC

civic

KRAS G12R

Regorafenib Anhydrous

Predictive

Supports Resistance

accepted

EID3991

In an in vitro study, a human colon adenocarcinoma SW48 cell line expressing KRAS G12R mutation demonstrated resistance to regorafenib treatment (IC50: 181.77 nM vs. 114.28 nM, P<0.01) compared to SW4… (full text at CIViC)

PMID 26161928 · Camaj et al., 2015 · Open in CIViC

civic

KRAS G12R

Sunitinib

Predictive

Supports Resistance

—

submitted

EID3992

In an in vitro study, colorectal cancer SW48 cell line expressing KRAS G12R mutation demonstrated reduced sensitivity to sunitinib treatment (IC50: 4.5uM vs. 2.6uM, P<0.05) compared to SW48 cells expr… (full text at CIViC)

PMID 23455880 · Modest et al., 2013 · Open in CIViC

civic

Malignant Pancreatic Neoplasm4
KRAS G12D AND KRAS G12R AND CDKN2A Loss AND CDKN2B Loss AND SMAD4 Deletion AND TP53 R267W	Bevacizumab + Palbociclib + TrametinibCombination	Predictive	C	Supports Sensitivity Response	3	submitted	EID11711 In this clinical trial, 18 patients with pancreatic cancer were recruited. In this case, the patient (63 y/F) with pancreatic cancer harboring, CDKN2A exons 1-2 loss, CDKN2B loss, KRAS G12D, KRAS G12R… (full text at CIViC) PMID 36670111 · Shaya et al., 2023 · Open in CIViC	civic
KRAS G12D AND KRAS G12R AND CDKN2A Loss AND CDKN2B Loss AND TP53 R267W	Bevacizumab + Palbociclib + TrametinibCombination	Predictive	C	Supports Sensitivity Response	3	submitted	EID11710 In this clinical trial, 18 patients with pancreatic cancer were recruited. In this case, the patient (69 y/M) with pancreatic cancer harboring, CDKN2A exons 1-2 loss, CDKN2B loss, KRAS G12D, KRAS G12R… (full text at CIViC) PMID 36670111 · Shaya et al., 2023 · Open in CIViC	civic
KRAS G12R	(prognostic)	Prognostic	B	Supports Poor Outcome	4	accepted	EID1298 In 242 patients with unresectable pancreatic cancer, the presence of KRAS G12R (N=17) or G12D (N=92) was associated with poorer prognosis (overall survival HR 1.6; 95% confidence interval 1.11-2.28). PMID 22983505 · Ogura et al., 2013 · Open in CIViC	civic
KRAS G12R	(prognostic)	Prognostic	B	Supports Poor Outcome	4	rejected	EID1299 In 242 patients with unresectable pancreatic cancer, the presence of KRAS G12R (as well as G12D) was associated with poorer prognosis (95% confidence interval of HR between 1.11 and 2.28). PMID 22983505 · Ogura et al., 2013 · Open in CIViC	civic

Malignant Pancreatic Neoplasm4

KRAS G12D AND KRAS G12R AND CDKN2A Loss AND CDKN2B Loss AND SMAD4 Deletion AND TP53 R267W

Bevacizumab + Palbociclib + TrametinibCombination

Predictive

Supports Sensitivity Response

submitted

EID11711

In this clinical trial, 18 patients with pancreatic cancer were recruited. In this case, the patient (63 y/F) with pancreatic cancer harboring, CDKN2A exons 1-2 loss, CDKN2B loss, KRAS G12D, KRAS G12R… (full text at CIViC)

PMID 36670111 · Shaya et al., 2023 · Open in CIViC

civic

KRAS G12D AND KRAS G12R AND CDKN2A Loss AND CDKN2B Loss AND TP53 R267W

Bevacizumab + Palbociclib + TrametinibCombination

Predictive

Supports Sensitivity Response

submitted

EID11710

In this clinical trial, 18 patients with pancreatic cancer were recruited. In this case, the patient (69 y/M) with pancreatic cancer harboring, CDKN2A exons 1-2 loss, CDKN2B loss, KRAS G12D, KRAS G12R… (full text at CIViC)

PMID 36670111 · Shaya et al., 2023 · Open in CIViC

civic

KRAS G12R

(prognostic)

Prognostic

Supports Poor Outcome

accepted

EID1298

In 242 patients with unresectable pancreatic cancer, the presence of KRAS G12R (N=17) or G12D (N=92) was associated with poorer prognosis (overall survival HR 1.6; 95% confidence interval 1.11-2.28).

PMID 22983505 · Ogura et al., 2013 · Open in CIViC

civic

KRAS G12R

(prognostic)

Prognostic

Supports Poor Outcome

rejected

EID1299

In 242 patients with unresectable pancreatic cancer, the presence of KRAS G12R (as well as G12D) was associated with poorer prognosis (95% confidence interval of HR between 1.11 and 2.28).

PMID 22983505 · Ogura et al., 2013 · Open in CIViC

civic

Malignant Thyroid Gland Neoplasm1
KRAS G12R	Dasatinib	Predictive	D	Supports Sensitivity Response	—	submitted	EID3997 In an in vitro study, a thyroid cancer cell line, CAL62, which harbors the KRAS G12R mutation, was associated with increased sensitivity to dasatinib treatment (IC50: 35nM). Sensitivity was determined… (full text at CIViC) PMID 22740998 · Chan et al., 2012 · Open in CIViC	civic

Malignant Thyroid Gland Neoplasm1

KRAS G12R

Dasatinib

Predictive

Supports Sensitivity Response

—

submitted

EID3997

In an in vitro study, a thyroid cancer cell line, CAL62, which harbors the KRAS G12R mutation, was associated with increased sensitivity to dasatinib treatment (IC50: 35nM). Sensitivity was determined… (full text at CIViC)

PMID 22740998 · Chan et al., 2012 · Open in CIViC

civic

Thyroid Gland Carcinoma1
KRAS G12R	Vemurafenib	Predictive	D	Supports Resistance	—	submitted	EID3999 In an in vitro study, a CAL62 cell line expressing KRAS G12R demonstrated reduced sensitivity to vemurafenib treatment, compared to BRAF V600E expressing cells (8505C, SWI1736, BHT101 and BCPAP). Sens… (full text at CIViC) PMID 19880792 · Salerno et al., 2010 · Open in CIViC	civic

Thyroid Gland Carcinoma1

KRAS G12R

Vemurafenib

Predictive

Supports Resistance

—

submitted

EID3999

In an in vitro study, a CAL62 cell line expressing KRAS G12R demonstrated reduced sensitivity to vemurafenib treatment, compared to BRAF V600E expressing cells (8505C, SWI1736, BHT101 and BCPAP). Sens… (full text at CIViC)

PMID 19880792 · Salerno et al., 2010 · Open in CIViC

civic

Histiocytosis-Lymphadenopathy Plus Syndrome2unmapped disease
KRAS G12R	Cobimetinib	Predictive	C	Supports Sensitivity Response	2	submitted	EID7310 A patient with Rosai-Dorfman disease havored KRAS G12R mutation were treated with cobimetinib. A perirenal soft-tissue mass (12cm by 11cm by 22cm) showed substantial response. PMID 29236635 · Jacobsen et al., 2017 · Open in CIViC	civic
KRAS G12R AND GATA3 Mutation AND GNAS Mutation	Cobimetinib	Predictive	C	Supports Sensitivity Response	2	submitted	EID11330 This case study is on a 60-year-old man with a 7-year history of fatigue that was noted to have a palpable abdominal mass while being seen for gastroesophageal reflux disease. A CT scan of the abdomen… (full text at CIViC) PMID 29236635 · Jacobsen et al., 2017 · Open in CIViC	civic

Histiocytosis-Lymphadenopathy Plus Syndrome2unmapped disease

KRAS G12R

Cobimetinib

Predictive

Supports Sensitivity Response

submitted

EID7310

A patient with Rosai-Dorfman disease havored KRAS G12R mutation were treated with cobimetinib. A perirenal soft-tissue mass (12cm by 11cm by 22cm) showed substantial response.

PMID 29236635 · Jacobsen et al., 2017 · Open in CIViC

civic

KRAS G12R AND GATA3 Mutation AND GNAS Mutation

Cobimetinib

Predictive

Supports Sensitivity Response

submitted

EID11330

This case study is on a 60-year-old man with a 7-year history of fatigue that was noted to have a palpable abdominal mass while being seen for gastroesophageal reflux disease. A CT scan of the abdomen… (full text at CIViC)

PMID 29236635 · Jacobsen et al., 2017 · Open in CIViC

civic

Solid Tumors, Advanced1unmapped disease
KRAS G12C OR KRAS G12D OR KRAS G13D OR RET M918T OR KRAS G12A OR KRAS G12V OR KRAS G12R OR KRAS Amplification OR KRAS G12S OR KRAS G13R OR KRAS G12P	Sorafenib	Predictive	B	Supports Sensitivity Response	3	submitted	EID12700 In the randomized discontinuation Phase II MOST-Plus trial of advanced/metastatic solid tumors with sorafenib-targeted somatic alterations (NCT02029001; n = 35 randomized; KRAS G12A/C/D/P/R/S/V n = 29… (full text at CIViC) PMID 37444551 · Trédan et al., 2023 · Open in CIViC	civic

Solid Tumors, Advanced1unmapped disease

KRAS G12C OR KRAS G12D OR KRAS G13D OR RET M918T OR KRAS G12A OR KRAS G12V OR KRAS G12R OR KRAS Amplification OR KRAS G12S OR KRAS G13R OR KRAS G12P

Sorafenib

Predictive

Supports Sensitivity Response

submitted

EID12700

In the randomized discontinuation Phase II MOST-Plus trial of advanced/metastatic solid tumors with sorafenib-targeted somatic alterations (NCT02029001; n = 35 randomized; KRAS G12A/C/D/P/R/S/V n = 29… (full text at CIViC)

PMID 37444551 · Trédan et al., 2023 · Open in CIViC

civic

Evidence by cancer (25 items)

Clinical significance (1)