PIK3CA E542K

Loading variant…

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Head and Neck Squamous Cell Carcinoma1
PIK3CA E542K	Apitolisib	Predictive	C	Supports Sensitivity Response	2	accepted	EID1549 Phase 1 study with the dual PI3K/mTOR inhibitor apitolisib. 120 patients were treated at doses between 2 and 70mg. Of the 14 evaluable patients with PIK3CA mutations total, there were 3 PRs (1 confirm… (full text at CIViC) PMID 26787751 · Dolly et al., 2016 · Open in CIViC	civic
HER2-Positive Breast Carcinoma3
PIK3CA E542K	PI-103	Predictive	D	Supports Sensitivity Response	1	accepted	EID2058 As part of a preclinical study, the efficacy of PI-103 (a dual inhibitor of MTOR and Class IA PI3Ks) was evaluated for several cell lines of breast cancer. Sensitivity and resistance was categorized a… (full text at CIViC)

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Head and Neck Squamous Cell Carcinoma1

PIK3CA E542K

Apitolisib

Predictive

Supports Sensitivity Response

accepted

EID1549

Phase 1 study with the dual PI3K/mTOR inhibitor apitolisib. 120 patients were treated at doses between 2 and 70mg. Of the 14 evaluable patients with PIK3CA mutations total, there were 3 PRs (1 confirm… (full text at CIViC)

PMID 26787751 · Dolly et al., 2016 · Open in CIViC

civic

HER2-Positive Breast Carcinoma3

PIK3CA E542K

PI-103

Predictive

Supports Sensitivity Response

accepted

EID2058

As part of a preclinical study, the efficacy of PI-103 (a dual inhibitor of MTOR and Class IA PI3Ks) was evaluated for several cell lines of breast cancer. Sensitivity and resistance was categorized a… (full text at CIViC)

Lung Non-Small Cell Carcinoma1
PIK3CA E542K	PI103	Predictive	D	Supports Sensitivity Response	—	submitted	EID2027 In H460, a gefitinib-resistant NSCLC cell line that harbors PIK3CA mutations, the dual PI3Kalpha/mTOR inhibitor PI103 reduced cell growth and increased the expression of the tumor suppressor p53 compa… (full text at CIViC) PMID 19513541 · Zou et al., 2009 · Open in CIViC	civic

Lung Non-Small Cell Carcinoma1

PIK3CA E542K

PI103

Predictive

Supports Sensitivity Response

—

submitted

EID2027

In H460, a gefitinib-resistant NSCLC cell line that harbors PIK3CA mutations, the dual PI3Kalpha/mTOR inhibitor PI103 reduced cell growth and increased the expression of the tumor suppressor p53 compa… (full text at CIViC)

PMID 19513541 · Zou et al., 2009 · Open in CIViC

civic

Malignant Breast Neoplasm9
PIK3CA E542K	Alpelisib + FulvestrantCombination	Predictive	A	Supports Sensitivity Response	3	accepted	EID7315 In a phase 3 trial, 572 patients with hormone receptor positive, HER2 receptor negative advanced breast cancer who previously received endocrine therapy were allocated to alpelisib plus fulvestrant or… (full text at CIViC) PMID 31091374 · André et al., 2019 · Open in CIViC	civic
PIK3CA E542K	Izorlisib	Predictive	D	Supports Sensitivity Response	4	accepted	EID310 Breast cancer cell lines with E542K/E545K mutations showed increased sensitivity to CH5132799 than cells with wild-type PIK3CA gene. PMID 21558396 · Tanaka et al., 2011 · Open in CIViC	civic
PIK3CA E542K	PI-103	Predictive	D	Supports Resistance	1	accepted	EID8007 As part of a preclinical study, the efficacy of PI-103 was evaluated for several cell lines of breast cancer. Sensitivity and resistance was categorized as less than and more than an IC50 of 1umol/L, … (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
PIK3CA E542K	PI3Ka/Di	Predictive	D	Supports Sensitivity Response	1	accepted	EID8016 As part of a preclinical study, the efficacy of PI3KA/Di—a selective inhibitor for the α (IC50 for p100α: 3nM) and δ (IC50 for p100δ: 20nM) subunits of class I PI3K—was evaluated for several cell line… (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
PIK3CA E542K	Pictilisib	Predictive	D	Supports Sensitivity Response	2	accepted	EID2026 This preclinical study tested the efficacy on several breast cancer cell lines of GDC-0941 (pictilisib), which is a selective inhibitor of all four isoforms of class I PI3-kinases over a range of IC50… (full text at CIViC) PMID 20453058 · O'Brien et al., 2010 · Open in CIViC	civic
PIK3CA E542K	Sirolimus	Predictive	D	Supports Sensitivity Response	3	accepted	EID311 Rapamycin inhibits transformation induced by mutation in PIK3CA. PMID 15647370 · Kang et al., 2005 · Open in CIViC	civic
PIK3CA E542K	Trastuzumab	Predictive	C	Supports Resistance	—	submitted	EID2024 In HER2-positive metastic breast cancer patients treated with trastuzumab-based therapy, the presence of a PIK3CA mutation was associated with an increased risk of progression (HR:2.50, 95% CI:1.35-4.… (full text at CIViC) PMID 21594665 · Razis et al., 2011 · Open in CIViC	civic
PIK3CA E542K OR PIK3CA E542Q OR PIK3CA E542A OR PIK3CA E542D OR PIK3CA E542G OR PIK3CA E542R OR PIK3CA E542V	Fulvestrant + Inavolisib + PalbociclibCombination	Predictive	A	Supports Sensitivity Response	3	accepted	EID12535 The phase III INAVO120 trial (NCT04191499) in 325 patients with endocrine-resistant, PIK3CA-mutated HR⁺/HER2⁻ locally advanced or metastatic breast cancer evaluated inavolisib plus palbociclib and ful… (full text at CIViC) PMID 40845250 · Wedam et al., 2025 · Open in CIViC	civic
PIK3CA E542K OR PIK3CA E545K OR PIK3CA H1047R	FAC Regimen + FEC RegimenSubstitutes	Predictive	B	Does Not Support Resistance	3	accepted	EID6191 This study of 140 patients with stage II-III breast cancer assessed the response of patients with PIK3CA mutations to 6 months of preoperative chemotherapy. Exons 1, 9, and 20 of PIK3CA were screened… (full text at CIViC) PMID 18371219 · Liedtke et al., 2008 · Open in CIViC	civic

Malignant Breast Neoplasm9

PIK3CA E542K

Alpelisib + FulvestrantCombination

Predictive

Supports Sensitivity Response

accepted

EID7315

In a phase 3 trial, 572 patients with hormone receptor positive, HER2 receptor negative advanced breast cancer who previously received endocrine therapy were allocated to alpelisib plus fulvestrant or… (full text at CIViC)

PMID 31091374 · André et al., 2019 · Open in CIViC

civic

PIK3CA E542K

Izorlisib

Predictive

Supports Sensitivity Response

accepted

EID310

Breast cancer cell lines with E542K/E545K mutations showed increased sensitivity to CH5132799 than cells with wild-type PIK3CA gene.

PMID 21558396 · Tanaka et al., 2011 · Open in CIViC

civic

PIK3CA E542K

PI-103

Predictive

Supports Resistance

accepted

EID8007

As part of a preclinical study, the efficacy of PI-103 was evaluated for several cell lines of breast cancer. Sensitivity and resistance was categorized as less than and more than an IC50 of 1umol/L, … (full text at CIViC)

PMID 20453058 · O'Brien et al., 2010 · Open in CIViC

civic

PIK3CA E542K

PI3Ka/Di

Predictive

Supports Sensitivity Response

accepted

EID8016

As part of a preclinical study, the efficacy of PI3KA/Di—a selective inhibitor for the α (IC50 for p100α: 3nM) and δ (IC50 for p100δ: 20nM) subunits of class I PI3K—was evaluated for several cell line… (full text at CIViC)

PMID 20453058 · O'Brien et al., 2010 · Open in CIViC

civic

PIK3CA E542K

Pictilisib

Predictive

Supports Sensitivity Response

accepted

EID2026

This preclinical study tested the efficacy on several breast cancer cell lines of GDC-0941 (pictilisib), which is a selective inhibitor of all four isoforms of class I PI3-kinases over a range of IC50… (full text at CIViC)

PMID 20453058 · O'Brien et al., 2010 · Open in CIViC

civic

PIK3CA E542K

Sirolimus

Predictive

Supports Sensitivity Response

accepted

EID311

Rapamycin inhibits transformation induced by mutation in PIK3CA.

PMID 15647370 · Kang et al., 2005 · Open in CIViC

civic

PIK3CA E542K

Trastuzumab

Predictive

Supports Resistance

—

submitted

EID2024

In HER2-positive metastic breast cancer patients treated with trastuzumab-based therapy, the presence of a PIK3CA mutation was associated with an increased risk of progression (HR:2.50, 95% CI:1.35-4.… (full text at CIViC)

PMID 21594665 · Razis et al., 2011 · Open in CIViC

civic

PIK3CA E542K OR PIK3CA E542Q OR PIK3CA E542A OR PIK3CA E542D OR PIK3CA E542G OR PIK3CA E542R OR PIK3CA E542V

Fulvestrant + Inavolisib + PalbociclibCombination

Predictive

Supports Sensitivity Response

accepted

EID12535

The phase III INAVO120 trial (NCT04191499) in 325 patients with endocrine-resistant, PIK3CA-mutated HR⁺/HER2⁻ locally advanced or metastatic breast cancer evaluated inavolisib plus palbociclib and ful… (full text at CIViC)

PMID 40845250 · Wedam et al., 2025 · Open in CIViC

civic

PIK3CA E542K OR PIK3CA E545K OR PIK3CA H1047R

FAC Regimen + FEC RegimenSubstitutes

Predictive

Does Not Support Resistance

accepted

EID6191

This study of 140 patients with stage II-III breast cancer assessed the response of patients with PIK3CA mutations to 6 months of preoperative chemotherapy. Exons 1, 9, and 20 of PIK3CA were screened… (full text at CIViC)

PMID 18371219 · Liedtke et al., 2008 · Open in CIViC

civic

Malignant Colorectal Neoplasm7
PIK3CA E542K	(prognostic)	Prognostic	B	Supports Poor Outcome	3	rejected	EID385 The presence of exon 9 (such as E542K) or exon 20 mutations were associated with poorer survival compared to those with wild-type PIK3CA mutation (P = 0.035). PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC	civic
PIK3CA E542K	Aspirin	Predictive	B	Supports Sensitivity Response	—	rejected	EID2032 In a study of 413 patients with colorectal cancer who were taking aspirin since diagnosis, the frequency of PIK3CA mutations was 17% (70/413). In 530 patients with colorectal cancer not using aspirin,… (full text at CIViC) PMID 23094721 · Liao et al., 2012 · Open in CIViC	civic
PIK3CA E542K	Aspirin	Predictive	B	Supports Sensitivity Response	—	submitted	EID2033 Phosphatidylinositol 3-kinase (PIK3CA) is composed of an 85kDa regulatory subunit and a 110kDa (p110alpha) catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which u… (full text at CIViC) PMID 9742087 · Klippel et al., 1998 · Open in CIViC	civic
PIK3CA E542K	Cetuximab	Predictive	C	Supports Resistance	—	rejected	EID3719 In colorectal cancer patients treated with salvage cetuximab therapy in combination with chemotherapy, PIK3CA mutations were associated with reduced progression-free survival (2.5mo vs. 3.9mo, HR:2.1,… (full text at CIViC) PMID 19603024 · Souglakos et al., 2009 · Open in CIViC	civic
PIK3CA E542K	Cetuximab	Predictive	C	Does Not Support Resistance	3	accepted	EID4424 This was a retrospective study of 691 cetuximab treated patients with metastatic colorectal cancer. Of those, 7 patients harbored PIK3CA E542K (exon 10), were wt for BRAF, NRAS and PIK3CA, and had ind… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
PIK3CA E542K	Cetuximab + PanitumumabSubstitutes	Predictive	B	Supports Resistance	3	rejected	EID256 The presence of a PIK3CA mutation in exon 9 (such as E542K) or exon 20 were associated with lack of panitumumab or cetuximab response. PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC	civic
PIK3CA E542K	Regorafenib Anhydrous	Predictive	B	Does Not Support Resistance	3	accepted	EID83 This was a retrospective analysis of genetic markers in 503 metastatic colorectal cancer patients who participated in the CORRECT phase III trial of regorafenib. PIK3CA mutations were identified in th… (full text at CIViC) PMID 26184520 · Tabernero et al., 2015 · Open in CIViC	civic

Malignant Colorectal Neoplasm7

PIK3CA E542K

(prognostic)

Prognostic

Supports Poor Outcome

rejected

EID385

The presence of exon 9 (such as E542K) or exon 20 mutations were associated with poorer survival compared to those with wild-type PIK3CA mutation (P = 0.035).

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

civic

PIK3CA E542K

Aspirin

Predictive

Supports Sensitivity Response

—

rejected

EID2032

In a study of 413 patients with colorectal cancer who were taking aspirin since diagnosis, the frequency of PIK3CA mutations was 17% (70/413). In 530 patients with colorectal cancer not using aspirin,… (full text at CIViC)

PMID 23094721 · Liao et al., 2012 · Open in CIViC

civic

PIK3CA E542K

Aspirin

Predictive

Supports Sensitivity Response

—

submitted

EID2033

Phosphatidylinositol 3-kinase (PIK3CA) is composed of an 85kDa regulatory subunit and a 110kDa (p110alpha) catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which u… (full text at CIViC)

PMID 9742087 · Klippel et al., 1998 · Open in CIViC

civic

PIK3CA E542K

Cetuximab

Predictive

Supports Resistance

—

rejected

EID3719

In colorectal cancer patients treated with salvage cetuximab therapy in combination with chemotherapy, PIK3CA mutations were associated with reduced progression-free survival (2.5mo vs. 3.9mo, HR:2.1,… (full text at CIViC)

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

civic

PIK3CA E542K

Cetuximab

Predictive

Does Not Support Resistance

accepted

EID4424

This was a retrospective study of 691 cetuximab treated patients with metastatic colorectal cancer. Of those, 7 patients harbored PIK3CA E542K (exon 10), were wt for BRAF, NRAS and PIK3CA, and had ind… (full text at CIViC)

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

civic

PIK3CA E542K

Cetuximab + PanitumumabSubstitutes

Predictive

Supports Resistance

rejected

EID256

The presence of a PIK3CA mutation in exon 9 (such as E542K) or exon 20 were associated with lack of panitumumab or cetuximab response.

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

civic

PIK3CA E542K

Regorafenib Anhydrous

Predictive

Does Not Support Resistance

accepted

EID83

This was a retrospective analysis of genetic markers in 503 metastatic colorectal cancer patients who participated in the CORRECT phase III trial of regorafenib. PIK3CA mutations were identified in th… (full text at CIViC)

PMID 26184520 · Tabernero et al., 2015 · Open in CIViC

civic

Malignant Gastric Neoplasm1
PIK3CA E542K AND PTEN Loss	Capivasertib	Predictive	D	Supports Sensitivity Response	2	submitted	EID11063 In a panel of 20 gastric cancer cell lines, the line that showed greatest sensitivity to AZD5363 in MTS cell proliferation assay contained both PIK3CA E542K and PTEN Loss. PMID 24088382 · Li et al., 2013 · Open in CIViC	civic

Malignant Gastric Neoplasm1

PIK3CA E542K AND PTEN Loss

Capivasertib

Predictive

Supports Sensitivity Response

submitted

EID11063

In a panel of 20 gastric cancer cell lines, the line that showed greatest sensitivity to AZD5363 in MTS cell proliferation assay contained both PIK3CA E542K and PTEN Loss.

PMID 24088382 · Li et al., 2013 · Open in CIViC

civic

Malignant Thyroid Gland Neoplasm1
PIK3CA E542K	Perifosine + TemsirolimusSubstitutes	Predictive	D	Supports Sensitivity Response	3	accepted	EID1626 Preclinical study in thyroid cancer cell lines. 6 cell lines with alterations of the PI3K/Akt pathway were more sensitive to Akt inhibitor perifosine or MTOR inhibitor temsirolimus than 5 cell lines w… (full text at CIViC) PMID 19706758 · Liu et al., 2009 · Open in CIViC	civic

Malignant Thyroid Gland Neoplasm1

PIK3CA E542K

Perifosine + TemsirolimusSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID1626

Preclinical study in thyroid cancer cell lines. 6 cell lines with alterations of the PI3K/Akt pathway were more sensitive to Akt inhibitor perifosine or MTOR inhibitor temsirolimus than 5 cell lines w… (full text at CIViC)

PMID 19706758 · Liu et al., 2009 · Open in CIViC

civic

HER2 Negative Breast Cancer1unmapped disease
PIK3CA E542K	Capivasertib + FulvestrantCombination	Predictive	A	Supports Sensitivity Response	2	submitted	EID12184 In a phase 3 trial (NCT04305496) of 708 patients with advanced HR+ HER2- breast cancer, the combination of the AKT inhibitor capivasertib and the estrogen receptor degrader fulvestrant resulted in sig… (full text at CIViC) PMID 37256976 · Turner et al., 2023 · Open in CIViC	civic

HER2 Negative Breast Cancer1unmapped disease

PIK3CA E542K

Capivasertib + FulvestrantCombination

Predictive

Supports Sensitivity Response

submitted

EID12184

In a phase 3 trial (NCT04305496) of 708 patients with advanced HR+ HER2- breast cancer, the combination of the AKT inhibitor capivasertib and the estrogen receptor degrader fulvestrant resulted in sig… (full text at CIViC)

PMID 37256976 · Turner et al., 2023 · Open in CIViC

civic

Evidence by cancer (24 items)

Clinical significance (0)