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| Profile Name | PIK3CA act mut |
| Gene Variant Detail | |
| Relevant Treatment Approaches | Akt Inhibitor (Pan) Akt1 Inhibitor Akt2 Inhibitor mTOR Inhibitor mTORC1 Inhibitor mTORC2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| PIK3CA mutant | breast cancer | sensitive | VS-5584 | Preclinical | Actionable | In a preclinical study, PIK3CA mutant breast cancer cells showed increased sensitivity to VS-5584 compared to PIK3CA wild-type cells in culture (PMID: 23270925). | 23270925 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | CUDC-907 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CUDC-907 inhibited PIK3CA, blocked downstream AKT pathway activation, and induced apoptosis and cell cycle arrest in both PIK3CA wild-type and PIK3CA mutant human cancer cell lines and xenograft models of multiple tumor types (PMID: 22693356). | 22693356 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | PX-866 | Phase I | Actionable | In a Phase I trial, PX-866 demonstrated efficacy and was well tolerated in patients with advanced solid tumor with both PIK3CA wild-type and mutant status (PMID: 22693357). | 22693357 |
| PIK3CA mutant | breast adenocarcinoma | sensitive | Acalisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Acalisib (GS-9820) resulted in tumor growth inhibition in xenograft models of breast adenocarcinoma harboring a PIK3CA mutation (Mol Cancer Ther 2009;8(12 Suppl):B136). | detail... |
| PIK3CA mutant | breast cancer | sensitive | Sapanisertib | Preclinical | Actionable | In a preclinical study, Sapanisertib (MLN0128) demonstrated efficacy in PIK3CA mutant breast cancer xenograft models (PMID: 23085766). | 23085766 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | M2698 | Preclinical | Actionable | In a preclinical study, MSC2363318A demonstrated anti-proliferative activity against many solid tumor cell lines with PI3K pathway genomic alterations, and inhibited tumor growth in several human cancer xenograft models of breast, pancreatic, glioblastoma and ovarian cancers (Mol Cancer Ther 2013;12(11 Suppl):A162). | detail... |
| PIK3CA mutant | colon cancer | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 demonstrated efficacy in promoting apoptosis of colon cancer cells harboring a PIK3CA mutation in culture (PMID: 22543857). | 22543857 |
| PIK3CA mutant | Her2-receptor positive breast cancer | sensitive | CCT128930 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CCT128930 induced growth arrest and inhibited tumor growth in a xenograft model of a ERBB2 (HER2)-positive human breast cancer cell line harboring a PIK3CA mutation (PMID: 21191045). | 21191045 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | XL147 | Phase I | Actionable | In a Phase I clinical trial, XL147 (SAR24508) was shown to be safe and potentially efficacious, with clinical activity seen irrespective of tumor PI3K pathway molecular alterations (PMID: 24166903). | 24166903 |
| PIK3CA mutant | hematologic cancer | sensitive | CUDC-907 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CUDC-907 inhibited PIK3CA, blocked downstream AKT pathway activation, and induced apoptosis and cell cycle arrest in both PIK3CA wild-type and PIK3CA mutant human cancer cell lines and xenograft models of multiple solid and hematologic cancers (PMID: 22693356). | 22693356 |
| PIK3CA mutant | squamous cell carcinoma | sensitive | Carboxyamidotriazole Orotate | Phase I | Actionable | In a Phase I clinical trial, carboxyamidotriazole orotate treatment demonstrated some efficacy in patients with various solid tumors including squamous cell carcinomas (tonsil) with PI3KCA and NRAS mutations (J Clin Oncol 31, 2013 (suppl; abstr 2518)). | detail... |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | Onatasertib | Phase I | Actionable | In a Phase I trial, CC-223 demonstrated safety and preliminary efficacy in patients with solid tumors, including stable disease for greater than 110 days in 2 patients with PIK3CA mutation or PTEN deletion (PMID: 26177599). | 26177599 detail... |
| PIK3CA mutant | ovarian cancer | sensitive | Temsirolimus | Phase I | Actionable | In a Phase I clinical trial, Torisel (temsirolimus) demonstrated limited efficacy in ovarian cancer patients with PIK3CA mutations (PMID: 22271473). | 22271473 |
| PIK3CA mutant | endometrioid ovary carcinoma | sensitive | Capivasertib | Case Reports/Case Series | Actionable | In a Phase I clinical trial, Truqap (capivasertib) demonstrated safety and efficacy in patients with advanced solid tumors, including prolonged stable disease (156 days) in one patient with a PIK3CA-mutant endometrioid ovarian cancer (Cancer Res 2013;73(8 Suppl):Abstract nr LB-66; NCT01226316, NCT01353781). | detail... |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | Alpelisib | Phase I | Actionable | In a Phase I trial, Alpelisib (BYL719) demonstrated safety and efficacy in patients with advanced solid tumor harboring PIK3CA mutations, resulted in a disease control rate of 58.2% (78/134, 1 complete response (CR), 7 partial response (PR), 70 stable disease (SD)), and a clinical benefit rate (CR+PR+SD>24 weeks) of 15.7% (21/134) (PMID: 29401002; NCT01219699). | 29401002 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | Carboxyamidotriazole Orotate | Phase I | Actionable | In a Phase I clinical trial, carboxyamidotriazole orotate treatment demonstrated some efficacy in patients with various solid tumors, including patients harboring PIK3CA mutations (J Clin Oncol 31, 2013 (suppl; abstr 2518)). | detail... |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | Serabelisib | Preclinical | Actionable | In a preclinical study, MLN1117 inhibited proliferation of tumor cells harboring oncogenic PIK3CA mutations in culture and inhibited tumor growth in PIK3CA mutant xenograft models (Cancer Ther 2011;10(11 Suppl):Abstract nr A171). | detail... |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | VS-5584 | Preclinical | Actionable | In preclinical studies, VS-5584 demonstrated efficacy in a variety of cancer cell lines, particularly those harboring PIK3CA mutations (PMID: 23270925). | 23270925 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | Sapanisertib | Preclinical | Actionable | In a preclinical study, human cancer cell lines harboring PIK3CA mutations were sensitive to Sapanisertib (MLN0128) as demonstrated by significant growth inhibition (PMID: 25261369). | 25261369 |
| PIK3CA mutant | breast cancer | predicted - sensitive | Capivasertib | Preclinical | Actionable | In a preclinical study, Truqap (capivasertib) inhibited growth in breast cancer cell lines and xenograft models expressing PIK3CA mutations (PMID: 22294718). | 22294718 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | BAY1082439 | Preclinical | Actionable | In a preclinical study, BAY1082439 induced regression in xenograft models of advanced solid tumors with PIK3CA mutations (Cancer Res April 15, 2012 72; 2799). | detail... |
| PIK3CA mutant | breast cancer | sensitive | Pictilisib | Preclinical | Actionable | In a preclinical study, GDC-0941 inhibited growth and induced apoptosis in breast cancer cells expressing PIK3CA mutations (PMID: 24601221). | 24601221 |
| PIK3CA mutant | breast cancer | no benefit | Temsirolimus | Phase II | Actionable | In a Phase II trial, Torisel (temsirolimus) treatment resulted in stable disease in 9.7% (3/31) of breast cancer patients positive for ER, PR or ERBB2 (HER2), however there was no association between PIK3CA mutational status and clinical benefits (PMID: 22245973). | 22245973 |
| PIK3CA mutant | breast cancer | sensitive | AZD8835 | Preclinical | Actionable | In a preclinical study, AZD8835 inhibited tumor growth in breast cancer xenograft models harboring PIK3CA mutations (AACR; 2015. Abstract nr 2665). | detail... |
| PIK3CA mutant | stomach cancer | sensitive | BAY1082439 | Preclinical | Actionable | In a preclinical study, BAY1082439 inhibited growth of gastric cancer cells harboring PIK3CA mutations in culture and xenograft models (AACR; 2015. Abstract nr 2674). | detail... |
| PIK3CA mutant | lung non-small cell carcinoma | sensitive | PWT33597 | Preclinical | Actionable | In a preclinical study, PWT33597 decreased signaling of mTOR and PIK3 pathways in non-small cell lung cancer cells with Pik3ca mutations (Cancer Res 2011;71(8 Suppl):Abstract nr 4485). | detail... |
| PIK3CA mutant | colon cancer | sensitive | PWT33597 | Preclinical | Actionable | In a preclinical study, PWT33597 decreased signaling of mTOR and PIK3 pathways in colon cancer cells with Pik3ca mutations (Cancer Res 2011;71(8 Suppl):Abstract nr 4485). | detail... |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | A-443654 | Preclinical | Actionable | In a preclinical study, cells expressing mutant PIK3CA demonstrated increased sensitivity to A-443654 compared to cells expressing wild-type PIK3CA (PMID: 19208828). | 19208828 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | AT-7867 | Preclinical | Actionable | In a preclinical study, AT-7867 inhibited proliferation in several human tumor cell lines harboring PIK3CA mutations in culture (PMID: 20423992). | 20423992 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | Serabelisib | Phase I | Actionable | In a Phase I trial, MLN1117 demonstrated safety and preliminary efficacy in a variety of patients with advanced solid tumors carrying PIK3CA mutations (Journal of Clinical Oncology, 2015 ASCO Annual Meeting Vol 33, No 15_suppl., 2015: 2501). | detail... |
| PIK3CA mutant | ovarian cancer | sensitive | OSI-027 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, OSI-027 inhibited tumor growth in ovarian cancer cell line xenograft models harboring PIK3CA mutations (PMID: 21673091). | 21673091 |
| PIK3CA mutant | gastric adenocarcinoma | sensitive | Fluorouracil + PI-103 | Preclinical | Actionable | In a preclinical study, PI-103 enhanced sensitivity to 5-FU in gastric cancer cells with mutant PIK3CA (PMID: 22336586). | 22336586 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | Taselisib | Phase I | Actionable | In a Phase I trial, Taselisib (GDC-0032) demonstrated activity in patients with PIK3CA-mutant advanced solid tumors, in the absence of alterations in the MAPK or PTEN pathways (Cancer Res October 1, 2014 74:915). | detail... |
| PIK3CA mutant | breast cancer | sensitive | MEN1611 | Preclinical | Actionable | In a preclinical study, breast cancer cells with PIK3CA mutations, both with and without ERBB2 (HER2) amplification, demonstrated sensitivity to MEN1611 (CH5132799) in culture (PMID: 21558396). | 21558396 |
| PIK3CA mutant | ovarian cancer | sensitive | MEN1611 | Preclinical | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited proliferation of ovarian cancer cells with PIK3CA mutations in culture (PMID: 21558396). | 21558396 |
| PIK3CA mutant | prostate cancer | sensitive | MEN1611 | Preclinical | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited proliferation of prostate cancer cells with PIK3CA mutations in culture (PMID: 21558396). | 21558396 |
| PIK3CA mutant | endometrial cancer | sensitive | MEN1611 | Preclinical | Actionable | In a preclinical study, MEN1611 (CH5132799) inhibited proliferation of endometrial cancer cells with PIK3CA mutations in culture (PMID: 21558396). | 21558396 |
| PIK3CA mutant | breast cancer | sensitive | CUDC-907 | Preclinical | Actionable | In a preclinical study, CUDC-907 inhibited growth of human breast cancer cell lines harboring PIK3CA mutations in culture (PMID: 22693356). | 22693356 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | Bevacizumab + Pegylated liposomal doxorubicin + Temsirolimus | Clinical Study | Actionable | In a clinical study, the combination of Torisel (temisirolimus) plus Avastin (bevacizumab) and Doxil (pegylated liposomal-doxirubicin) resulted in stable disease in patients with advanced solid tumors harboring PIK3CA mutations (PMID: 21216929). | 21216929 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | Bevacizumab + Pegylated liposomal doxorubicin + Temsirolimus | Clinical Study | Actionable | In a clinical study, the combination of Torisel (temsirolimus) plus Avastin (bevacizumab) and Doxil (pegylated liposomal-doxorubicin) resulted in a partial response in patients with advanced solid tumors harboring PIK3CA mutations (PMID: 21216929). | 21216929 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | AZD8835 | Preclinical | Actionable | In a preclinical study, AZD8835 inhibited growth of a variety of advanced solid tumor models with Pik3ca mutations in culture (PMID: 26839307). | 26839307 |
| PIK3CA mutant | cervical cancer | decreased response | Cetuximab | Phase II | Actionable | In a Phase II clinical trial, Erbitux (cetuximab) treatment, in addition to radiochemotherapy, did not result in any complete responses (0/8) and demonstrated a worse disease free survival when compared to radiochemotherapy alone in cervical cancer patients harboring PIK3CA mutations (PMID: 25724520). | 25724520 |
| PIK3CA mutant | Advanced Solid Tumor | predicted - sensitive | Uprosertib | Phase I | Actionable | In a Phase I clinical trial, GSK2141795 demonstrated safety and preliminary efficacy in patients with advanced solid tumors, with 4 patients with PIK3CA mutations and/or PTEN loss achieving stable disease for greater than 6 months (J Clin Oncol 29: 2011 (suppl; abstr 3003)). | detail... |
| PIK3CA mutant | head and neck squamous cell carcinoma | sensitive | Radiotherapy + Taselisib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Taselisib (GDC-0032) enhanced the effects of radiation induced apoptosis in HNSCC cell lines, cell line xenograft models, and a patient derived xenograft (PDX) model, all with PIK3CA mutations (PMID: 26589432). | 26589432 |
| PIK3CA mutant | stomach cancer | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 demonstrated efficacy in promoting apoptosis of gastric cancer cells harboring a PIK3CA mutation in culture (PMID: 22543857). | 22543857 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | Alpelisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PIK3CA mutations were associated with sensitivity to Alpelisib (BYL719) in human tumor cell lines in culture and in xenograft models (PMID: 24608574). | 24608574 |
| PIK3CA mutant | endometrial cancer | sensitive | Pictilisib | Preclinical | Actionable | In a preclinical study, endometrioid endometrial cancer cell lines harboring PIK3CA mutations demonstrated increased sensitivity to GDC-0941 (Pictilisib) induced growth inhibition comparing to PIK3CA wild-type cells in culture (PMID: 23674493). | 23674493 |
| PIK3CA mutant | estrogen-receptor positive breast cancer | sensitive | AZD8835 | Preclinical | Actionable | In a preclinical study, AZD8835 inhibited proliferation of estrogen receptor (ER)-positive breast cancer cells harboring PIK3CA mutations in culture and suppressed tumor growth in xenograft models (PMID: 26839307). | 26839307 |
| PIK3CA mutant | endometrial cancer | sensitive | Apitolisib | Phase II | Actionable | In a Phase II trial, Apitolisib (GDC-0980) was poorly tolerated, but demonstrated efficacy in endometrial cancer patients harboring mutations in PIK3CA, PTEN, or AKT1 (J Clin Oncol 32:5s, 2014 (suppl; abstr 5513)). | detail... |
| PIK3CA mutant | Advanced Solid Tumor | predicted - sensitive | Apitolisib | Case Reports/Case Series | Actionable | In a Phase I trial, Apitolisib (GDC-0980) treatment resulted in a partial response in 21% (3/14) and stable disease in 64% (9/14) of patients with advanced solid tumors harboring PIK3CA mutations (PMID: 26787751; NCT00854152). | 26787751 |
| PIK3CA mutant | breast cancer | no benefit | GSK2126458 | Phase I | Actionable | In a Phase I trial, GSK2126458 was well-tolerated and resulted in some efficacy in patients with breast cancer harboring a PIK3CA mutation including stable disease in 22% (2/9), however, objective response rate was not associated with PIK3CA mutations when compared to those without PIK3CA mutations (PMID: 26603258). | 26603258 |
| PIK3CA mutant | triple-receptor negative breast cancer | sensitive | Palbociclib + Pictilisib | Preclinical | Actionable | In a preclinical study, Ibrance (palbociclib) and Pictilisib (GDC-0941) worked synergistically to inhibit the survival of triple-receptor negative breast cancer cell lines harboring PIK3CA mutations in culture (PMID: 27020857). | 27020857 |
| PIK3CA mutant | Advanced Solid Tumor | sensitive | XL147 | Preclinical | Actionable | In a preclinical study, tumor cell lines with PIK3CA mutations demonstrated sensitivity to XL147 in culture (PMID: 25637314). | 25637314 |
| PIK3CA mutant | breast cancer | sensitive | Letrozole + Taselisib | Phase Ib/II | Actionable | In a Phase Ib trial, Taselisib (GDC-0032) and Femara (letrozole) combination therapy resulted in an overall response rate of 38% in breast cancer patients with PIK3CA mutations, compared to 9% in patients with wild-type PIK3CA (Cancer Res May 1, 2015 75; PD5-2). | detail... |
| PIK3CA mutant | endometrial cancer | no benefit | Temsirolimus | Phase II | Actionable | In a retrospective study of a Phase II trial, mutation status of PIK3CA was not associated with progression-free survival or response rate in advanced endometrial cancer patients treated with Torisel (temsirolimus) (PMID: 27016228). | 27016228 |
| PIK3CA mutant | ovarian cancer | sensitive | Buparlisib + Olaparib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Buparlisib (BKM120) and Lynparza (olaparib) worked synergistically to induce apoptosis and inhibit growth of ovarian cancer cell lines harboring PIK3CA mutations in culture, and induced apoptosis and decreased proliferation of PIK3CA-mutant ovarian cancer cell line xenograft models (PMID: 26909613). | 26909613 |
| PIK3CA mutant | estrogen-receptor positive breast cancer | no benefit | Fulvestrant + Pictilisib | Phase II | Actionable | In a Phase II trial, Falsodex (fulvestrant) and Pictilisib (GDC-0941) combination treatment resulted in similar progression free survival in ER positive breast cancer patients harboring PIK3CA mutations and those who were PIK3CA wild-type (PMID: 27174596). | 27174596 |
| PIK3CA mutant | estrogen-receptor positive breast cancer | no benefit | Fulvestrant | Phase II | Actionable | In a Phase II trial, Falsodex (fulvestrant) treatment resulted in similar progression free survival in ER positive breast cancer patients harboring PIK3CA mutations and those who were PIK3CA wild-type (PMID: 27174596). | 27174596 |
| PIK3CA mutant | breast cancer | sensitive | Alpelisib + GSK2334470 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, GSK2334470 resensitized Alpelisib (BYL719)-resistant breast cancer cell lines harboring PIK3CA mutations to Alpelisib (BYL719) in culture and in cell line xenograft models (PMID: 27451907). | 27451907 |
| PIK3CA mutant | triple-receptor negative breast cancer | sensitive | Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, triple-receptor negative breast cancer cell lines harboring PIK3CA mutations demonstrated increased sensitivity to Pictilisib (GDC-0941) in culture (PMID: 27196766). | 27196766 |
| PIK3CA mutant | lung non-small cell carcinoma | sensitive | PF-04691502 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PF-04691502 inhibited tumor growth in non-small cell lung cancer cell line xenograft models harboring PIK3CA mutations (PMID: 21750219). | 21750219 |
| PIK3CA mutant | colorectal cancer | predicted - sensitive | MS417 + Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, Pictilisib (GDC-0941) and MS417 in combination resulted in improved growth inhibition and increased cell death compared to either agent alone in colorectal cancer cell lines harboring PIK3CA mutations in culture (PMID: 26058079). | 26058079 |
| PIK3CA mutant | breast cancer | sensitive | OSI-027 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, OSI-027 induced tumor regression in breast cancer cell line xenograft models harboring PIK3CA mutations (PMID: 21673091). | 21673091 |
| PIK3CA mutant | invasive bladder transitional cell carcinoma | predicted - resistant | Cisplatin + Gemcitabine + Sorafenib | Phase II | Actionable | In a Phase II trial, PIK3CA mutations were more frequent in muscle-invasive urothelial bladder cancer patients that did not respond to Nexavar (sorafenib), Platinol (cisplatin) and Gemzar (gemcitabine) combination therapy than those who did respond (J Clin Oncol 35, 2017 (suppl 6S; abstract 345)). | detail... |
| PIK3CA mutant | breast cancer | sensitive | AT13148 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a ERBB3 (HER3) positive breast cancer cell line xenograft model harboring a PIK3CA mutation was demonstrated decreased tumor growth when treated with AT13148 (PMID: 22781553). | 22781553 |
| PIK3CA mutant | breast cancer | predicted - sensitive | Serabelisib | Case Reports/Case Series | Actionable | In a Phase I trial, MLN1117 (INK1117) treatment resulted in partial response in 3 patients with breast cancer harboring PI3CA mutations (PMID: 28490463; NCT01449370). | 28490463 |
| PIK3CA mutant | stomach cancer | predicted - sensitive | Serabelisib | Case Reports/Case Series | Actionable | In a Phase I trial, MLN1117 (INK1117) treatment resulted in a partial response in one patient with gastric cancer harboring a PIK3CA mutation (PMID: 28490463; NCT01449370). | 28490463 |
| PIK3CA mutant | Her2-receptor negative breast cancer | no benefit | Capivasertib + Paclitaxel | Phase II | Actionable | In a Phase II trial, the addition of Truqap (capivasertib) to Taxol (paclitaxel) therapy did not improve progression-free survival compared to placebo (10.9 vs 10.8 months) in patients with PIK3CA-mutant, Esr1-positive, Erbb2 (Her2)-negative breast cancer (PMID: 30860570; NCT01625286). | 30860570 |
| PIK3CA mutant | head and neck squamous cell carcinoma | predicted - sensitive | Carboplatin + Paclitaxel + Temsirolimus | Phase II | Actionable | In a Phase II trial, two patients with head and neck squamous cell carcinoma harboring a PIK3CA mutation who had stable disease demonstrated some tumor regression when treated with the combination of Torisel (temsirolimus), Paraplatin (carboplatin), and Taxol (paclitaxel) (PMID: 28961834). | 28961834 |
| PIK3CA mutant | breast cancer | predicted - sensitive | Inavolisib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Itovebi (inavolisib) inhibited proliferation and induced apoptosis in PIK3CA-mutant breast cancer cell lines in culture, and induced apoptosis and tumor regression in PIK3CA-mutant breast cancer cell line and patient-derived xenograft models (AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 156). | detail... |
| PIK3CA mutant | breast cancer | predicted - sensitive | Capivasertib | Phase I | Actionable | In a Phase I trial, treatment with Truqap (capivasertib) was well-tolerated and resulted in tumor shrinkage in 46% (12/26) patients with PIK3CA-mutant breast cancer, with confirmed RECIST responses in 4% (1/28) of patients (PMID: 29066505; NCT01226316). | 29066505 |
| PIK3CA mutant | female reproductive organ cancer | predicted - sensitive | Capivasertib | Phase I | Actionable | In a Phase I trial, treatment with Truqap (capivasertib) was well-tolerated and resulted in tumor shrinkage in 56% (14/25) patients with PIK3CA-mutant gynecological cancers, however, the response rate was modest with confirmed RECIST responses in 8% (2/26) of patients (PMID: 29066505; NCT01226316). | 29066505 |
| PIK3CA mutant | Her2-receptor negative breast cancer | sensitive | Alpelisib | Phase I | Actionable | In a Phase I trial, Alpelisib (BYL719) treatment resulted in a disease control rate of 60.9% (14/23, 0 complete response (CR), 1 partial response (PR), 13 stable disease (SD)), and a clinical benefit rate (CR+PR+SD>24 weeks) of 17.4% (4/23) in patients with ER-positive, ERBB2 (HER2)-negative breast cancer harboring PIK3CA mutations (PMID: 29401002; NCT01219699). | 29401002 |
| PIK3CA mutant | head and neck cancer | sensitive | Alpelisib | Phase I | Actionable | In a Phase I trial, Alpelisib (BYL719) treatment resulted in a disease control rate of 68.4% (13/19, 0 complete response (CR), 0 partial response (PR), 13 stable disease (SD)), and a clinical benefit rate (CR+PR+SD>24 weeks) of 10.5% (2/19) in patients with head and neck cancer harboring PIK3CA mutations (PMID: 29401002; NCT01219699). | 29401002 |
| PIK3CA mutant | colorectal cancer | sensitive | Alpelisib | Phase I | Actionable | In a Phase I trial, Alpelisib (BYL719) treatment resulted in a disease control rate of 34.3% (12/35, 0 complete response (CR), 2 partial response (PR), 10 stable disease (SD)), and a clinical benefit rate (CR+PR+SD>24 weeks) of 8.6% (3/35) in patients with colorectal cancer harboring PIK3CA mutations (PMID: 29401002; NCT01219699). | 29401002 |
| PIK3CA mutant | endometrial cancer | sensitive | Alpelisib | Case Reports/Case Series | Actionable | In a Phase I trial, Alpelisib (BYL719) treatment resulted in 1 complete response and 1 partial response in patients with endometrial cancer harboring PIK3CA mutations (PMID: 29401002; NCT01219699). | 29401002 |
| PIK3CA mutant | cervical cancer | predicted - sensitive | Alpelisib | Case Reports/Case Series | Actionable | In a Phase I trial, Alpelisib (BYL719) treatment resulted in partial response in 3 patients with cervical cancer harboring PIK3CA mutations (PMID: 29401002; NCT01219699). | 29401002 |
| PIK3CA mutant | estrogen-receptor positive breast cancer | predicted - sensitive | Letrozole | Phase III | Actionable | In a Phase III trial, estrogen-receptor positive breast cancer patients harboring a PIK3CA mutation demonstrated a greater benefit when treated with Femara (letrozole) compared to Nolvadex (tamoxifen) (PMID: 29902286; NCT00004205). | 29902286 |
| PIK3CA mutant | hepatocellular carcinoma | decreased response | Sorafenib | Clinical Study - Cohort | Actionable | In a clinical case study, Nexavar (sorafenib) treatment of patients with hepatocellular carcinoma harboring Mtor pathway mutations in PIK3CA, PTEN, TSC2, or TSC1 (n=12), resulted in a lower disease control rate (8.3% vs. 40.2%), shorter progression-free survival (1.9 months vs. 5.3 months) and shorter overall survival (10.4 months vs. 17.9 months) compared to patients without mutations in this pathway (n=67) (PMID: 30373752; NCT01775072). | 30373752 |
| PIK3CA mutant | ovarian cancer | sensitive | Temsirolimus | Case Reports/Case Series | Actionable | In a clinical study, an ovarian cancer patient harboring a PIK3CA E542 mutation demonstrated stable disease when treated with Torisel (temsirolimus) (PMID: 21216929). | 21216929 |
| PIK3CA mutant | lung squamous cell carcinoma | no benefit | Taselisib | Phase I | Actionable | In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet its primary endpoint for response rate in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in only 1 response in the primary analysis population (n=21) (PMID: 31158500; NCT02785913). | 31158500 |
| PIK3CA mutant | breast cancer | no benefit | MK2206 | Phase II | Actionable | In a Phase II trial, MK2206 demonstrated limited clinical efficacy in patients with advanced breast cancer harboring mutations in PIK3CA (n=14) or AKT1 (n=4), resulted in an objective response rate of 5.6% (1/18, 1 partial response) and a 6-month progression-free survival rate of 5.6%, with no significant target inhibition in tumor biopsies (PMID: 31277699; NCT01277757). | 31277699 |
| PIK3CA mutant | Advanced Solid Tumor | no benefit | Alpelisib + Infigratinib | Phase Ib/II | Actionable | In a Phase Ib trial, treatment with the combination of Piqray (alpelisib) and Truseltiq (infigratinib) resulted in partial response (PR) in 9.7% (6/62) and disease control (PR or stable disease) in 61.3% (34/62) of patients with advanced solid tumors harboring a PIK3CA mutation with or without an FGFR alteration, however, the efficacy was not deemed great enough to pursue further development (JCO Precision Oncology 2019 :3, 1-13). | detail... |
| PIK3CA mutant | breast cancer | predicted - sensitive | CYH33 | Preclinical - Cell culture | Actionable | In a preclinical study, breast cancer cell lines harboring PIK3CA mutations demonstrated increased sensitivity to CYH33 compared to cell lines with wild-type PIK3CA in culture (p<0.01) (PMID: 30003928). | 30003928 |
| PIK3CA mutant | Her2-receptor negative breast cancer | no benefit | Everolimus | Phase III | Actionable | In a retrospective analysis of a Phase III trial (BOLERO-2), the presence of PIK3CA mutations did not significantly affect the efficacy of Afinitor (everolimus) in patients with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer, with a HR for progression-free survival of 0.37 in PIK3CA wild-type group and a HR of 0.51 (p=0.35) in patients with PIK3CA mutations (PMID: 26503204; NCT00863655). | 26503204 |
| PIK3CA mutant | endometrial carcinoma | no benefit | Copanlisib | Phase II | Actionable | In a Phase II (NRG-GY008) trial, Aliqopa (copanlisib) was well tolerated but demonstrated limited efficacy, resulted in stable disease as best response in 54.5% (6/11) of patients with endometrial carcinoma harboring PIK3CA mutations, with a median progression-free survival of 2.8 months and a median overall survival of 15.2 months (PMID: 31934607). | 31934607 |
| PIK3CA mutant | lung non-small cell carcinoma | predicted - sensitive | Sulindac | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cell lines harboring either a PIK3CA mutation or PIK3CA amplification demonstrated increased sensitivity to Clinoril (sulindac) compared to cell lines with wild-type PIK3CA, resulting in decreased proliferation in culture (PMID: 30683736). | 30683736 |
| PIK3CA mutant | endometrial cancer | no benefit | MK2206 | Phase II | Actionable | In a Phase II trial, MK2206 demonstrated limited benefit in endometrial cancer patients regardless of PIK3CA status, with partial responses in 6% (2/37) of patients, 19% (7/37; 5 with serous histology) remaining progression-free for at least 6 mo, and a median progression-free survival (PFS) of 2.0 mo in the overall population, and partial responses in 11% (11/9), 33% (3/9) progression-free for 6 mo, and a median PFS of 1.7 mo in the group of patients with PIK3CA mutations (PMID: 31714586; NCT01307631). | 31714586 |
| PIK3CA mutant | Her2-receptor positive breast cancer | not predictive | Ado-trastuzumab emtansine | Phase III | Actionable | In a retrospective analysis of a Phase III trial (KATHERINE), adjuvant Kadcyla (ado-trastuzumab emtansine) treatment demonstrated similar invasive disease-free survival benefit over Herceptin (trastuzumab) in PIK3CA mutant (HR=0.54) and PIK3CA wild-type (HR=0.48) patients with Erbb2 (Her2)-positive breast cancer who had residual invasive disease after neoadjuvant therapy (PMID: 36730339; NCT01772472). | 36730339 |
| PIK3CA mutant | ovarian cancer | not predictive | Perifosine | Phase II | Actionable | In a Phase II trial , Perifosine (KRX-0401) treatment was well-tolerated, resulted in stable disease as best response in patients with recurrent ovarian cancer, no significant difference in disease control rate (12.5%, 2/16 vs 40%, 2/5, p=0.22), median progression-free survival (HR=0.57, p=0.32), or median overall survival (HR=1.37, p=0.58) was identified between PIK3CA wild-type and PIK3CA mutant patients (PMID: 28864978). | 28864978 |
| PIK3CA mutant | endometrial cancer | not predictive | Perifosine | Phase II | Actionable | In a Phase II trial , Perifosine (KRX-0401) treatment was well-tolerated, resulted in stable disease as best response in patients with recurrent endometrial cancer, no significant difference in disease control rate (47.1%, 8/17 vs 14.3%, 1/7, p=0.19), median progression-free survival (HR=1.71, p=0.30), or median overall survival (HR=0.92, p=0.88) was identified between PIK3CA wild-type and PIK3CA mutant patients (PMID: 28864978). | 28864978 |
| PIK3CA mutant | cervical cancer | not predictive | Perifosine | Phase II | Actionable | In a Phase II trial , Perifosine (KRX-0401) treatment was well-tolerated, resulted in stable disease as best response in patients with recurrent cervical cancer, no significant difference in disease control rate (11.1%, 2/18 vs 25%, 2/8, p=0.56), median progression-free survival (HR=1.06, p=0.81), or median overall survival (HR=1.66, p=0.26) was identified between PIK3CA wild-type and PIK3CA mutant patients (PMID: 28864978). | 28864978 |
| PIK3CA mutant | lung squamous cell carcinoma | no benefit | Capivasertib | Case Reports/Case Series | Actionable | In a Phase II trial (NLMT), Truqap (capivasertib) treatment did not result in a confirmed response (0/4) or durable clinical benefit (0/4) in patients with squamous cell lung cancer harboring PIK3CA mutations, thus the cohort was closed due to futility (PMID: 32669708, NCT02664935). | 32669708 |
| PIK3CA mutant | lung adenocarcinoma | no benefit | Capivasertib | Case Reports/Case Series | Actionable | In a Phase II trial (NLMT), Truqap (capivasertib) treatment did not result in a confirmed response (0/8) or durable clinical benefit (0/8) in patients with lung adenocarcinoma harboring mutations in PIK3CA, PTEN, or AKT, thus the cohort was closed due to futility (PMID: 32669708, NCT02664935). | 32669708 |
| PIK3CA mutant | Erdheim-Chester disease | sensitive | Sirolimus | Guideline | Actionable | Rapamune (sirolimus) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring PIK3CA mutations (NCCN.org). | detail... |
| PIK3CA mutant | Erdheim-Chester disease | sensitive | Everolimus | Guideline | Actionable | Afinitor (everolimus) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring PIK3CA mutations (NCCN.org). | detail... |
| PIK3CA mutant | Erdheim-Chester disease | sensitive | Cobimetinib | Guideline | Actionable | Cotellic (cobimetinib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org). | detail... |
| PIK3CA mutant | Erdheim-Chester disease | sensitive | Trametinib | Guideline | Actionable | Mekinist (trametinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org). | detail... |
| PIK3CA mutant | head and neck cancer | predicted - sensitive | WX390 | Case Reports/Case Series | Actionable | In a Phase I trial, WX390 treatment resulted in a partial responses in a patient with head and neck cancer harboring PIK3CA mutation, and stable disease with tumor shrinkage for 8 months in another patient with PIK3CA-mutant head and neck cancer (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 3106-3106; NCT03730142). | detail... |
| PIK3CA mutant | cervical cancer | predicted - sensitive | WX390 | Case Reports/Case Series | Actionable | In a Phase I trial, WX390 treatment resulted in a partial responses in a patient with cervical cancer harboring PIK3CA mutation (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 3106-3106; NCT03730142). | detail... |
| PIK3CA mutant | Advanced Solid Tumor | predicted - sensitive | TOS-358 | Preclinical - Pdx | Actionable | In a preclinical study, TOS-358 demonstrated efficacy in patient-derived xenograft (PDX) and cell line xenograft models harboring PIK3CA mutations (Cancer Res (2023) 83 (7_Supplement): 4946). | detail... |
| PIK3CA mutant | breast cancer | no benefit | Temsirolimus | Phase II | Actionable | In a Phase II trial (TAPUR), Torisel (temsirolimus) treatment demonstrated limited efficacy in patients with breast cancer harboring PIK3CA mutations, resulting in an objective response rate of 9% (1/12, 1 partial response) and a disease control rate of 9%, which let to the closing of the cohort due to futility (p=0.83) (J Clin Oncol 41, 2023 (suppl 16; abstr 3117); NCT02693535). | detail... |
| PIK3CA mutant | Ewing sarcoma | predicted - sensitive | Irinotecan + Temozolomide + Temsirolimus | Case Reports/Case Series | Actionable | In a clinical study, Torisel (temsirolimus), Temodar (temozolomide), and Camptosar (irinotecan) combination treatment resulted in a partial response in a pediatric patient with Ewing sarcoma harboring a PIK3CA mutation (PMID: 37523146; NCT03336931). | 37523146 |
| PIK3CA mutant | Ewing sarcoma | predicted - sensitive | Temsirolimus | Preclinical - Pdx | Actionable | In a preclinical study, Torisel (temsirolimus) treatment increased event-free survival in a Ewing sarcoma patient-derived xenograft (PDX) model harboring a PIK3CA mutation (PMID: 37523146). | 37523146 |
| PIK3CA mutant | colorectal cancer | predicted - sensitive | Copanlisib + Nivolumab | Phase Ib/II | Actionable | In a Phase I/II trial, treatment with the combination of Aliqopa (copanlisib) and Opdivo (nivolumab) was well tolerated and resulted in 3 partial responses in 22 patients with microsatellite stable colorectal cancer harboring PIK3CA mutations (Cancer Res (2024) 84 (7_Supplement): CT007; NCT03711058). | detail... |