KRAS G12A

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Lung Adenocarcinoma1
KRAS G12A	Erlotinib + GefitinibSubstitutes	Predictive	B	Supports Resistance	3	accepted	EID251 KRAS mutations (N=29 G12, N=1 G13) were the primary predictor of EGFR TKI resistance in patients with lung adenocarcinoma (N=83). Overall survival (P=0.001) and progression-free survival (P=0.005) wer… (full text at CIViC) PMID 19794967 · Marchetti et al., 2009 · Open in CIViC	civic
Lung Non-Small Cell Carcinoma2
KRAS G12A	Erlotinib	Predictive	C	Supports Resistance	—	submitted	EID3714 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…

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Lung Adenocarcinoma1

KRAS G12A

Erlotinib + GefitinibSubstitutes

Predictive

Supports Resistance

accepted

EID251

KRAS mutations (N=29 G12, N=1 G13) were the primary predictor of EGFR TKI resistance in patients with lung adenocarcinoma (N=83). Overall survival (P=0.001) and progression-free survival (P=0.005) wer… (full text at CIViC)

PMID 19794967 · Marchetti et al., 2009 · Open in CIViC

civic

Lung Non-Small Cell Carcinoma2

KRAS G12A

Erlotinib

Predictive

Supports Resistance

—

submitted

EID3714

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…

Malignant Colon Neoplasm1
KRAS G12A	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3717 In a phase 3 clinical study,�BRAF wild-type stage III colon cancer patients harboring KRAS G12A mutation (n=49) and treated with cetuximab plus standard chemotherapy were associated with decreased dis… (full text at CIViC) PMID 24687927 · Yoon et al., 2014 · Open in CIViC	civic

Malignant Colon Neoplasm1

KRAS G12A

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3717

In a phase 3 clinical study,�BRAF wild-type stage III colon cancer patients harboring KRAS G12A mutation (n=49) and treated with cetuximab plus standard chemotherapy were associated with decreased dis… (full text at CIViC)

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

civic

Malignant Colorectal Neoplasm18
KRAS G12A	Cetuximab	Predictive	B	Supports Resistance	3	accepted	EID4429 This was a retrospective study of 691 cetuximab treated patients with metastatic colorectal cancer. Of those, 22 patients harbored KRAS G12A, were BRAF, NRAS and PIK3CA wt, and had individual response… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
KRAS G12A	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3699 In a retrospective study of 30 metastatic colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation (n=13) treated with cetuximab and standard chemotherapy were associated with an absen… (full text at CIViC) PMID 16618717 · Lièvre et al., 2006 · Open in CIViC	civic
KRAS G12A	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3700 In a retrospective study of 113 metastatic irinotecan-refractory colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation treated with cetuximab plus irinotecan (34/83) were associated… (full text at CIViC) PMID 17998284 · De Roock et al., 2008 · Open in CIViC	civic
KRAS G12A	Cetuximab	Predictive	C	Supports Resistance	—	rejected	EID3701 In a retrospective study of 168 metastatic colorectal cancer patients, patients with a KRAS exon 2 mutation (32/92) treated with second-line or higher cetuximab therapy in combination with standard ch… (full text at CIViC) PMID 19603024 · Souglakos et al., 2009 · Open in CIViC	civic
KRAS G12A	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3702 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 G12A	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3703 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 G12A	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3705 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 G12A	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3706 In a phase 3 clinical study of 1,198 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFIRI were associated with reduced overal… (full text at CIViC) PMID 21502544 · Van Cutsem et al., 2011 · Open in CIViC	civic
KRAS G12A	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3707 In a phase 2 clinical study of 344 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFOX-4 (n=52) were associated with reduced … (full text at CIViC) PMID 19114683 · Bokemeyer et al., 2009 · Open in CIViC	civic
KRAS G12A	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3708 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 G12A	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3709 In a phase 3 clinical study (NCT00154102) of 1198 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFIRI (n=105) were associate… (full text at CIViC) PMID 19339720 · Van Cutsem et al., 2009 · Open in CIViC	civic
KRAS G12A	Cetuximab + PanitumumabSubstitutes	Predictive	C	Supports Resistance	2	accepted	EID6319 In this study, a large cohort of metastatic colorectal cancer patients were treated with anti-epidermal growth factor receptor monoclonal antibodies (cetuximab or panitumumab). KRAS, PIK3CA, and PTEN … (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC	civic
KRAS G12A	Panitumumab	Predictive	C	Supports Resistance	—	rejected	EID2005 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 16953233 · Oliveira et al., 2007 · Open in CIViC	civic
KRAS G12A	Panitumumab	Predictive	C	Supports Resistance	—	rejected	EID2006 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 2547513 · Bos, 1989 · Open in CIViC	civic
KRAS G12A	Panitumumab	Predictive	C	Supports Resistance	—	rejected	EID2007 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 8462792 · Benhattar et al., 1993 · Open in CIViC	civic
KRAS G12A	Cetuximab + PanitumumabSubstitutes	Predictive	C	Supports Resistance	2	submitted	EID6325 KRAS G12A was the only variant noted in the primary tumor of one metastatic colorectal cancer patient who experienced stable disease following treatment with anti-epidermal growth factor receptor (EGF… (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC	civic
KRAS G12A	Regorafenib Anhydrous	Predictive	D	Supports Resistance	2	accepted	EID3710 In an in vitro study, a human colon adenocarcinoma SW48 cell line virally transduced to express KRAS G12A demonstrated resistance to regorafenib treatment (IC50: 330.13 nM vs. 114.28 nM, P<0.01, repor… (full text at CIViC) PMID 26161928 · Camaj et al., 2015 · Open in CIViC	civic
KRAS G12A	Sunitinib	Predictive	D	Supports Resistance	—	submitted	EID3711 In an in vitro study, colorectal cancer SW48 cell line expressing KRAS G12A mutation demonstrated reduced sensitivity to sunitinib treatment (IC50: 6.5uM 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 Neoplasm18

KRAS G12A

Cetuximab

Predictive

Supports Resistance

accepted

EID4429

This was a retrospective study of 691 cetuximab treated patients with metastatic colorectal cancer. Of those, 22 patients harbored KRAS G12A, were BRAF, NRAS and PIK3CA wt, and had individual response… (full text at CIViC)

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

civic

KRAS G12A

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3699

In a retrospective study of 30 metastatic colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation (n=13) treated with cetuximab and standard chemotherapy were associated with an absen… (full text at CIViC)

PMID 16618717 · Lièvre et al., 2006 · Open in CIViC

civic

KRAS G12A

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3700

In a retrospective study of 113 metastatic irinotecan-refractory colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation treated with cetuximab plus irinotecan (34/83) were associated… (full text at CIViC)

PMID 17998284 · De Roock et al., 2008 · Open in CIViC

civic

KRAS G12A

Cetuximab

Predictive

Supports Resistance

—

rejected

EID3701

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

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

civic

KRAS G12A

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3702

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 G12A

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3703

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 G12A

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3705

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 G12A

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3706

In a phase 3 clinical study of 1,198 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFIRI were associated with reduced overal… (full text at CIViC)

PMID 21502544 · Van Cutsem et al., 2011 · Open in CIViC

civic

KRAS G12A

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3707

In a phase 2 clinical study of 344 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFOX-4 (n=52) were associated with reduced … (full text at CIViC)

PMID 19114683 · Bokemeyer et al., 2009 · Open in CIViC

civic

KRAS G12A

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3708

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 G12A

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3709

In a phase 3 clinical study (NCT00154102) of 1198 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFIRI (n=105) were associate… (full text at CIViC)

PMID 19339720 · Van Cutsem et al., 2009 · Open in CIViC

civic

KRAS G12A

Cetuximab + PanitumumabSubstitutes

Predictive

Supports Resistance

accepted

EID6319

In this study, a large cohort of metastatic colorectal cancer patients were treated with anti-epidermal growth factor receptor monoclonal antibodies (cetuximab or panitumumab). KRAS, PIK3CA, and PTEN … (full text at CIViC)

PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC

civic

KRAS G12A

Panitumumab

Predictive

Supports Resistance

—

rejected

EID2005

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

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

civic

KRAS G12A

Panitumumab

Predictive

Supports Resistance

—

rejected

EID2006

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

PMID 2547513 · Bos, 1989 · Open in CIViC

civic

KRAS G12A

Panitumumab

Predictive

Supports Resistance

—

rejected

EID2007

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

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

civic

KRAS G12A

Cetuximab + PanitumumabSubstitutes

Predictive

Supports Resistance

submitted

EID6325

KRAS G12A was the only variant noted in the primary tumor of one metastatic colorectal cancer patient who experienced stable disease following treatment with anti-epidermal growth factor receptor (EGF… (full text at CIViC)

PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC

civic

KRAS G12A

Regorafenib Anhydrous

Predictive

Supports Resistance

accepted

EID3710

In an in vitro study, a human colon adenocarcinoma SW48 cell line virally transduced to express KRAS G12A demonstrated resistance to regorafenib treatment (IC50: 330.13 nM vs. 114.28 nM, P<0.01, repor… (full text at CIViC)

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

civic

KRAS G12A

Sunitinib

Predictive

Supports Resistance

—

submitted

EID3711

In an in vitro study, colorectal cancer SW48 cell line expressing KRAS G12A mutation demonstrated reduced sensitivity to sunitinib treatment (IC50: 6.5uM 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 Lung Neoplasm2
KRAS G12A	Erlotinib	Predictive	C	Supports Resistance	—	submitted	EID3712 In locally advanced or metastic (stage IIIB or IV) non-small cell lung cancer patients with KRAS mutations, those treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib … (full text at CIViC) PMID 16043828 · Eberhard et al., 2005 · Open in CIViC	civic
KRAS G12A	Gefitinib	Predictive	B	Supports Resistance	2	accepted	EID2008 In recurrent lung cancer patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib, patients with KRAS mutations had a lower frequency of partial response (PR) and… (full text at CIViC) PMID 17409929 · Endoh et al., 2006 · Open in CIViC	civic

Malignant Lung Neoplasm2

KRAS G12A

Erlotinib

Predictive

Supports Resistance

—

submitted

EID3712

In locally advanced or metastic (stage IIIB or IV) non-small cell lung cancer patients with KRAS mutations, those treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib … (full text at CIViC)

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

civic

KRAS G12A

Gefitinib

Predictive

Supports Resistance

accepted

EID2008

In recurrent lung cancer patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib, patients with KRAS mutations had a lower frequency of partial response (PR) and… (full text at CIViC)

PMID 17409929 · Endoh et al., 2006 · Open in CIViC

civic

Multiple Myeloma6
KRAS G12A	Melphalan	Predictive	B	Supports Resistance	2	accepted	EID2009 In a study of patients receiving melphalan-based therapy, those with KRAS codon 12 mutations were less likely to have a positive response than those with wildtype KRAS (26.9% vs. 58.3%, P=0.015). PMID 19284554 · Greco et al., 2009 · Open in CIViC	civic
KRAS G12A	Melphalan	Predictive	B	Supports Resistance	—	submitted	EID2010 Activating mutations in KRAS or NRAS were observed more frequently in multiple myeloma patients than in patients with monoclonal gammopathy of uncertain significance (MGUS) (31% vs. 5% ). Another stu… (full text at CIViC) PMID 11524732 · Bezieau et al., 2001 · Open in CIViC	civic
KRAS G12A	Melphalan	Predictive	B	Supports Resistance	—	submitted	EID2011 Activating mutations in KRAS or NRAS were observed more frequently in multiple myeloma patients than in patients with monoclonal gammopathy of uncertain significance (MGUS) (31% vs. 5% ). Another stu… (full text at CIViC) PMID 15339850 · Rasmussen et al., 2005 · Open in CIViC	civic
KRAS G12A	Melphalan	Predictive	D	Supports Resistance	2	accepted	EID2012 In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC) PMID 11050000 · Rowley et al., 2000 · Open in CIViC	civic
KRAS G12A	Melphalan	Predictive	D	Supports Resistance	2	accepted	EID2013 In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC) PMID 12483530 · Rowley et al., 2002 · Open in CIViC	civic
KRAS G12A	Melphalan	Predictive	D	Supports Resistance	2	accepted	EID2014 In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC) PMID 16497971 · Hoang et al., 2006 · Open in CIViC	civic

Multiple Myeloma6

KRAS G12A

Melphalan

Predictive

Supports Resistance

accepted

EID2009

In a study of patients receiving melphalan-based therapy, those with KRAS codon 12 mutations were less likely to have a positive response than those with wildtype KRAS (26.9% vs. 58.3%, P=0.015).

PMID 19284554 · Greco et al., 2009 · Open in CIViC

civic

KRAS G12A

Melphalan

Predictive

Supports Resistance

—

submitted

EID2010

Activating mutations in KRAS or NRAS were observed more frequently in multiple myeloma patients than in patients with monoclonal gammopathy of uncertain significance (MGUS) (31% vs. 5% ). Another stu… (full text at CIViC)

PMID 11524732 · Bezieau et al., 2001 · Open in CIViC

civic

KRAS G12A

Melphalan

Predictive

Supports Resistance

—

submitted

EID2011

PMID 15339850 · Rasmussen et al., 2005 · Open in CIViC

civic

KRAS G12A

Melphalan

Predictive

Supports Resistance

accepted

EID2012

In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC)

PMID 11050000 · Rowley et al., 2000 · Open in CIViC

civic

KRAS G12A

Melphalan

Predictive

Supports Resistance

accepted

EID2013

PMID 12483530 · Rowley et al., 2002 · Open in CIViC

civic

KRAS G12A

Melphalan

Predictive

Supports Resistance

accepted

EID2014

PMID 16497971 · Hoang et al., 2006 · 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

Unmapped disease2unmapped disease
KRAS G12A	(functional)	Functional	D	Supports Gain Of Function	5	submitted	EID12973 KRAS p.Gly12Ala (NM_004985.5:c.35G>C causes decreased GTPase activity, and based on BRAF-RBD co-IP assay increased BRAF binding affinity. PMID 26037647 · Hunter et al., 2015 · Open in CIViC	civic
KRAS G12A	(functional)	Functional	D	Supports Gain Of Function	5	submitted	EID12974 KRAS p.Gly12Ala (NM_004985.5:c.35G>C causes increased pERK/ERK ratio. PMID 23455880 · Modest et al., 2013 · Open in CIViC	civic

Unmapped disease2unmapped disease

KRAS G12A

(functional)

Functional

Supports Gain Of Function

submitted

EID12973

KRAS p.Gly12Ala (NM_004985.5:c.35G>C causes decreased GTPase activity, and based on BRAF-RBD co-IP assay increased BRAF binding affinity.

PMID 26037647 · Hunter et al., 2015 · Open in CIViC

civic

KRAS G12A

(functional)

Functional

Supports Gain Of Function

submitted

EID12974

KRAS p.Gly12Ala (NM_004985.5:c.35G>C causes increased pERK/ERK ratio.

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

civic

Evidence by cancer (33 items)

Clinical significance (0)