Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings

Christine M Bestvina, Gini F Fleming, Christine M Bestvina, Gini F Fleming

Abstract

: Level I evidence exists for use of adjuvant chemotherapy in stage IIIC endometrial cancer (positive lymph nodes), although results of randomized trials have varied. Chemotherapy is also often recommended for high-risk subsets of stage I disease, such as serous carcinomas, although prospective trial data to validate this practice are lacking. Carboplatin plus paclitaxel is the current standard regimen, based on extrapolation of data from the metastatic setting. Several clinical trials have compared adjuvant pelvic radiotherapy alone to a combination of radiotherapy and chemotherapy with mixed results. One of the largest of these trials, Postoperative Radiation Therapy in Endometrial Carcinoma 3 (PORTEC-3), has completed accrual and is awaiting data maturation. Metastatic disease is not curable. For tumors of low-grade endometrioid histology with a prolonged time to recurrence, endocrine therapy with a progestin-based regimen is appropriate. Chemotherapy will be used in most other cases, and the standard first-line regimen is carboplatin and paclitaxel. Few chemotherapy agents have been shown to produce meaningful response rates in the second-line setting. Molecularly targeted therapies such as mTOR inhibitors and antiangiogenic agents including bevacizumab have been studied but their role in the armamentarium remains uncertain.

Implications for practice: Following surgical resection and staging for endometrial cancer, adjuvant chemotherapy with carboplatin and paclitaxel can be administered to patients with a high risk for recurrence. This includes patients with stage IIIC disease with positive lymph nodes, and high-risk subsets of stage I disease such as serous carcinomas. In the metastatic setting, endocrine therapy can be considered, particularly for patients with lower-grade disease and a prolonged time to recurrence. Combined therapy with carboplatin and paclitaxel is the standard of care used for front-line chemotherapy. Antiangiogenic agents are clearly active, but how they should be integrated into treatment is not yet determined. Immunotherapy is a promising direction for patients with mismatch repair-deficient or polymerase ε-mutated tumors.

Keywords: Chemoradiotherapy; Drug therapy, adjuvant; Endometrial cancer; Local neoplasm recurrence; Metastasis, neoplasm.

Conflict of interest statement

of potential conflicts of interest may be found at the end of this article.

©AlphaMed Press.

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.
    1. National Cancer Institute. Previous version: SEER Cancer Statistics Review, 1975-2012, National Cancer Institute. Available at . Accessed October 5, 2015.
    1. Hamilton CA, Cheung MK, Osann K, et al. Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer. 2006;94:642–646.
    1. Benedetti Panici P, Basile S, Maneschi F, et al. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: Randomized clinical trial. J Natl Cancer Inst. 2008;100:1707–1716.
    1. National Comprehensive Cancer Network. Uterine neoplasms. Available at . Accessed November 1, 2015.
    1. Amant F, Mirza MR, Koskas M, et al. Cancer of the corpus uteri. Int J Gynaecol Obstet. 2015;131(suppl 2):S96–S104.
    1. Poulsen H, Jacobsen M, Bertelsen K, et al. Adjuvant radiation therapy is not necessary in the management of endometrial carcinoma stage I, low risk cases. Int J Gynecol Cancer. 1996;6:38–43.
    1. Martin-Hirsch PP, Bryant A, Keep SL, et al. Adjuvant progestagens for endometrial cancer. Cochrane Database Syst Rev. 2011;(6):CD001040.
    1. Kong A, Johnson N, Kitchener HC, et al. Adjuvant radiotherapy for stage I endometrial cancer: An updated Cochrane systematic review and meta-analysis. J Natl Cancer Inst. 2012;104:1625–1634.
    1. Creutzberg CL, van Putten WL, Koper PC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: Multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet. 2000;355:1404–1411.
    1. Nout RA, Smit VT, Putter H, et al. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): An open-label, non-inferiority, randomised trial. Lancet. 2010;375:816–823.
    1. Meyer LA, Bohlke K, Powell MA, et al. Postoperative radiation therapy for endometrial cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Guideline. J Clin Oncol. 2015;33:2908–2913.
    1. Randall ME, Filiaci VL, Muss H, et al. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: A Gynecologic Oncology Group Study. J Clin Oncol. 2006;24:36–44.
    1. Maggi R, Lissoni A, Spina F, et al. Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: Results of a randomised trial. Br J Cancer. 2006;95:266–271.
    1. Susumu N, Sagae S, Udagawa Y, et al. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: A Japanese Gynecologic Oncology Group study. Gynecol Oncol. 2008;108:226–233.
    1. Kuoppala T, Mäenpää J, Tomas E, et al. Surgically staged high-risk endometrial cancer: Randomized study of adjuvant radiotherapy alone vs. sequential chemo-radiotherapy. Gynecol Oncol. 2008;110:190–195.
    1. Hogberg T, Signorelli M, de Oliveira CF, et al. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies. Eur J Cancer. 2010;46:2422–2431.
    1. McMeekin DSFV, Aghajanian C, Cho J, et al. Randomized phase III trial of pelvic radiation therapy (PXRT) versus vaginal cuff brachytherapy followed by paclitaxel/carboplatin chemotherapy (VCB/C) in patients with high risk (HR), early stage endometrial cancer (EC): A Gynecologic Oncology Group trial. Gynecol Oncol. 2014;134:438.
    1. Fleming GF. Systemic chemotherapy for uterine carcinoma: Metastatic and adjuvant. J Clin Oncol. 2007;25:2983–2990.
    1. Miller D, Filiaci V, Fleming G, et al. Randomized phase III noninferiority trial of first line chemotherapy for metastatic or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2012;125:771.
    1. Homesley HD, Filiaci V, Gibbons SK, et al. A randomized phase III trial in advanced endometrial carcinoma of surgery and volume directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: A Gynecologic Oncology Group study. Gynecol Oncol. 2009;112:543–552.
    1. Kandoth C, Schultz N, Cherniack AD, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497:67–73.
    1. McConechy MK, Talhouk A, Leung S, et al. Endometrial carcinomas with POLE exonuclease domain mutations have a favorable prognosis. Clin Cancer Res. 2016;22:2865–2873.
    1. McMeekin DS, Filiaci VL, Thigpen JT, et al. The relationship between histology and outcome in advanced and recurrent endometrial cancer patients participating in first-line chemotherapy trials: A Gynecologic Oncology Group study. Gynecol Oncol. 2007;106:16–22.
    1. Creutzberg CL, de Boer SM, Putter H, et al. Adjuvant chemotherapy and radiation therapy (RT) versus RT alone for women with high-risk endometrial cancer: Toxicity and quality-of-life results of the randomized PORTEC-3 trial. J Clin Oncol. 2015;33(suppl):abstr 5501.
    1. Mountzios G, Pectasides D, Bournakis E, et al. Developments in the systemic treatment of endometrial cancer. Crit Rev Oncol Hematol. 2011;79:278–292.
    1. Singh M, Zaino RJ, Filiaci VJ, et al. Relationship of estrogen and progesterone receptors to clinical outcome in metastatic endometrial carcinoma: A Gynecologic Oncology Group Study. Gynecol Oncol. 2007;106:325–333.
    1. Ma BB, Oza A, Eisenhauer E, et al. The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers--a study of the National Cancer Institute of Canada Clinical Trials Group. Int J Gynecol Cancer. 2004;14:650–658.
    1. Thigpen JT, Blessing JA, DiSaia P, et al. Oral medroxyprogesterone acetate in advanced or recurrent endometrial carcinoma: Results of therapy and correlation with estrogen and progesterone receptor levels— The Gynecologic Oncology Group experience. In: Baulier E, Iacobelli S, McGuire W, editors. Endocrinology and Malignancy. Pearl River, NY: Parthenon Publishers; 1986. pp. 446–454.
    1. Thigpen JT, Brady MF, Alvarez RD, et al. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: A dose-response study by the Gynecologic Oncology Group. J Clin Oncol. 1999;17:1736–1744.
    1. Thigpen T, Brady MF, Homesley HD, et al. Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. J Clin Oncol. 2001;19:364–367.
    1. McMeekin DS, Gordon A, Fowler J, et al. A phase II trial of arzoxifene, a selective estrogen response modulator, in patients with recurrent or advanced endometrial cancer. Gynecol Oncol. 2003;90:64–69.
    1. Rose PG, Brunetto VL, VanLe L, et al. A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2000;78:212–216.
    1. Covens AL, Filiaci V, Gersell D, et al. Phase II study of fulvestrant in recurrent/metastatic endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2011;120:185–188.
    1. Emons G, Günthert A, Thiel FC, et al. Phase II study of fulvestrant 250 mg/month in patients with recurrent or metastatic endometrial cancer: A study of the Arbeitsgemeinschaft Gynäkologische Onkologie. Gynecol Oncol. 2013;129:495–499.
    1. Gallagher CJ, Oliver RT, Oram DH, et al. A new treatment for endometrial cancer with gonadotrophin releasing-hormone analogue. Br J Obstet Gynaecol. 1991;98:1037–1041.
    1. Jeyarajah AR, Gallagher CJ, Blake PR, et al. Long-term follow-up of gonadotrophin-releasing hormone analog treatment for recurrent endometrial cancer. Gynecol Oncol. 1996;63:47–52.
    1. Lhommé C, Vennin P, Callet N, et al. A multicenter phase II study with triptorelin (sustained-release LHRH agonist) in advanced or recurrent endometrial carcinoma: A French Anticancer Federation Study. Gynecol Oncol. 1999;75:187–193.
    1. Asbury RF, Brunetto VL, Lee RB, et al. Goserelin acetate as treatment for recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Am J Clin Oncol. 2002;25:557–560.
    1. Pandya KJ, Yeap BY, Weiner LM, et al. Megestrol and tamoxifen in patients with advanced endometrial cancer: An Eastern Cooperative Oncology Group Study (E4882) Am J Clin Oncol. 2001;24:43–46.
    1. Whitney CW, Brunetto VL, Zaino RJ, et al. Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2004;92:4–9.
    1. Fiorica JV, Brunetto VL, Hanjani P, et al. Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2004;92:10–14.
    1. Thigpen JT, Blessing JA, DiSaia PJ, et al. A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. J Clin Oncol. 1994;12:1408–1414.
    1. van Wijk FH, Aapro MS, Bolis G, et al. Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: Definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group. Ann Oncol. 2003;14:441–448.
    1. Thigpen JT, Brady MF, Homesley HD, et al. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: A Gynecologic Oncology Group study. J Clin Oncol. 2004;22:3902–3908.
    1. Fleming GF, Filiaci VL, Bentley RC, et al. Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: A Gynecologic Oncology Group study. Ann Oncol. 2004;15:1173–1178.
    1. Fleming GF, Brunetto VL, Cella D, et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: A Gynecologic Oncology Group Study. J Clin Oncol. 2004;22:2159–2166.
    1. Dimopoulos MA, Papadimitriou CA, Georgoulias V, et al. Paclitaxel and cisplatin in advanced or recurrent carcinoma of the endometrium: Long-term results of a phase II multicenter study. Gynecol Oncol. 2000;78:52–57.
    1. Hoskins PJ, Swenerton KD, Pike JA, et al. Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: A phase II study. J Clin Oncol. 2001;19:4048–4053.
    1. Pignata S, Scambia G, Pisano C, et al. A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma: the END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) group. Br J Cancer. 2007;96:1639–1643.
    1. Aghajanian C, Filiaci VL, Dizon DS, et al. A randomized phase II study of paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus and ixabepilone/carboplatin/bevacizumab as initial therapy for measurable stage III or IVA, stage IVB or recurrent endometrial cancer, GOG-86P. J Clin Oncol. 2015;33(suppl):abstr 5500.
    1. Lorusso D, Ferrandina G, Colombo N, et al. Randomized phase II trial of carboplatin-paclitaxel (CP) compared to carboplatin-paclitaxel-bevacizumab (CP-B) in advanced (stage III-IV) or recurrent endometrial cancer: The MITO END-2 trial. J Clin Oncol. 2015;33(suppl):abstr 5502.
    1. Homesley HD, Meltzer NP, Nieves L, et al. A phase II trial of weekly 1-hour paclitaxel as second-line therapy for endometrial and cervical cancer. Int J Clin Oncol. 2008;13:62–65.
    1. Lincoln S, Blessing JA, Lee RB, et al. Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2003;88:277–281.
    1. Lissoni A, Zanetta G, Losa G, et al. Phase II study of paclitaxel as salvage treatment in advanced endometrial cancer. Ann Oncol. 1996;7:861–863.
    1. Markman M, Blessing J, Rubin SC, et al. Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: A Gynecologic Oncology Group study. Gynecol Oncol. 2006;101:436–440.
    1. Fracasso PM, Blessing JA, Molpus KL, et al. Phase II study of oxaliplatin as second-line chemotherapy in endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2006;103:523–526.
    1. Gupta D, Owers RL, Kim M, et al. A phase II study of weekly topotecan and docetaxel in heavily treated patients with recurrent uterine and ovarian cancers. Gynecol Oncol. 2009;113:327–330.
    1. Miller DS, Blessing JA, Lentz SS, et al. A phase II trial of topotecan in patients with advanced, persistent, or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2002;87:247–251.
    1. Muggia FM, Blessing JA, Sorosky J, et al. Phase II trial of the pegylated liposomal doxorubicin in previously treated metastatic endometrial cancer: A Gynecologic Oncology Group study. J Clin Oncol. 2002;20:2360–2364.
    1. Rose PG, Blessing JA, Lewandowski GS, et al. A phase II trial of prolonged oral etoposide (VP-16) as second-line therapy for advanced and recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 1996;63:101–104.
    1. Pawinski A, Tumolo S, Hoesel G, et al. Cyclophosphamide or ifosfamide in patients with advanced and/or recurrent endometrial carcinoma: A randomized phase II study of the EORTC Gynecological Cancer Cooperative Group. Eur J Obstet Gynecol Reprod Biol. 1999;86:179–183.
    1. Miller DS, Blessing JA, Drake RD, et al. A phase II evaluation of pemetrexed (Alimta, LY231514, IND #40061) in the treatment of recurrent or persistent endometrial carcinoma: A phase II study of the Gynecologic Oncology. Gynecol Oncol. 2009;115:443–446.
    1. Tait DL, Blessing JA, Hoffman JS, et al. A phase II study of gemcitabine (gemzar, LY188011) in the treatment of recurrent or persistent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2011;121:118–121.
    1. Sutton GP, Blessing JA, Homesley HD, et al. Phase II study of ifosfamide and mesna in refractory adenocarcinoma of the endometrium. A Gynecologic Oncology Group study. Cancer. 1994;73:1453–1455.
    1. Dizon DS, Blessing JA, McMeekin DS, et al. Phase II trial of ixabepilone as second-line treatment in advanced endometrial cancer: Gynecologic Oncology Group trial 129-P. J Clin Oncol. 2009;27:3104–3108.
    1. McMeekin S, Dizon D, Barter J, et al. Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer. Gynecol Oncol. 2015;138:18–23.
    1. Nagao S, Nishio S, Michimae H, et al. Applicability of the concept of “platinum sensitivity” to recurrent endometrial cancer: The SGSG-012/GOTIC-004/Intergroup study. Gynecol Oncol. 2013;131:567–573.
    1. Husseinzadeh N, Husseinzadeh HD. mTOR inhibitors and their clinical application in cervical, endometrial and ovarian cancers: A critical review. Gynecol Oncol. 2014;133:375–381.
    1. Myers AP. New strategies in endometrial cancer: Targeting the PI3K/mTOR pathway--the devil is in the details. Clin Cancer Res. 2013;19:5264–5274.
    1. McMeekin DS, Sill MW, Benbrook D, et al. A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study. Gynecol Oncol. 2007;105:508–516.
    1. Nimeiri HS, Oza AM, Morgan RJ, et al. A phase II study of sorafenib in advanced uterine carcinoma/carcinosarcoma: A trial of the Chicago, PMH, and California Phase II Consortia. Gynecol Oncol. 2010;117:37–40.
    1. Aghajanian C, Sill MW, Darcy KM, et al. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: A Gynecologic Oncology Group study. J Clin Oncol. 2011;29:2259–2265.
    1. Coleman RL, Sill MW, Lankes HA, et al. A phase II evaluation of aflibercept in the treatment of recurrent or persistent endometrial cancer: A Gynecologic Oncology Group study. Gynecol Oncol. 2012;127:538–543.
    1. Vergote I, Teneriello M, Powell MA, et al. A phase II trial of lenvatinib in patients with advanced or recurrent endometrial cancer: Angiopoietin-2 as a predictive marker for clinical outcomes. J Clin Oncol. 2013;31(suppl):abstr 5520.
    1. Castonguay V, Lheureux S, Welch S, et al. A phase II trial of sunitinib in women with metastatic or recurrent endometrial carcinoma: A study of the Princess Margaret, Chicago and California Consortia. Gynecol Oncol. 2014;134:274–280.
    1. Powell MA, Sill MW, Goodfellow PJ, et al. A phase II trial of brivanib in recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group Study. Gynecol Oncol. 2014;135:38–43.
    1. Dizon DS, Sill MW, Schilder JM, et al. A phase II evaluation of nintedanib (BIBF-1120) in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group Study. Gynecol Oncol. 2014;135:441–445.
    1. Bender D, Sill MW, Lankes HA, et al. A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2015;138:507–512.
    1. Moore KN, Sill MW, Tenney ME, et al. A phase II trial of trebananib (AMG 386; IND#111071), a selective angiopoietin 1/2 neutralizing peptibody, in patients with persistent/recurrent carcinoma of the endometrium: An NRG/Gynecologic Oncology Group trial. Gynecol Oncol. 2015;138:513–518.
    1. Slomovitz BM, Lu KH, Johnston T, et al. A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma. Cancer. 2010;116:5415–5419.
    1. Ray-Coquard I, Favier L, Weber B, et al. Everolimus as second- or third-line treatment of advanced endometrial cancer: ENDORAD, a phase II trial of GINECO. Br J Cancer. 2013;108:1771–1777.
    1. Oza AM, Elit L, Tsao MS, et al. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: A trial of the NCIC Clinical Trials Group. J Clin Oncol. 2011;29:3278–3285.
    1. Fleming GF, Filiaci VL, Marzullo B, et al. Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: A Gynecologic Oncology Group study. Gynecol Oncol. 2014;132:585–592.
    1. Colombo N, McMeekin DS, Schwartz PE, et al. Ridaforolimus as a single agent in advanced endometrial cancer: Results of a single-arm, phase 2 trial. Br J Cancer. 2013;108:1021–1026.
    1. Oza AM, Pignata S, Poveda A, et al. Randomized phase II trial of ridaforolimus in advanced endometrial carcinoma. J Clin Oncol. 2015;33:3576–3582.
    1. Alvarez EA, Brady WE, Walker JL, et al. Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2013;129:22–27.
    1. Slomovitz BM, Jiang Y, Yates MS, et al. Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma. J Clin Oncol. 2015;33:930–936.
    1. Oza AM, Eisenhauer EA, Elit L, et al. Phase II study of erlotinib in recurrent or metastatic endometrial cancer: NCIC IND-148. J Clin Oncol. 2008;26:4319–4325.
    1. Fleming GF, Sill MW, Darcy KM, et al. Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2010;116:15–20.
    1. Slomovitz B, Schmeler K, Miller D, et al. Phase II study of cetuximab (Erbitux) in patients with progressive or recurrent endometrial cancer. Gynecol Oncol. 2010;116:S2–S169.
    1. Leslie KK, Sill MW, Lankes HA, et al. Lapatinib and potential prognostic value of EGFR mutations in a Gynecologic Oncology Group phase II trial of persistent or recurrent endometrial cancer. Gynecol Oncol. 2012;127:345–350.
    1. Leslie KK, Sill MW, Fischer E, et al. A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: A Gynecologic Oncology Group study. Gynecol Oncol. 2013;129:486–494.
    1. Myers AP, Filiaci VL, Zhang Y, et al. Tumor mutational analysis of GOG248, a phase II study of temsirolimus or temsirolimus and alternating megestrol acetate and tamoxifen for advanced endometrial cancer (EC): An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2016;141:43–48.
    1. Pant A, Lee II, Lu Z, et al. Inhibition of AKT with the orally active allosteric AKT inhibitor, MK-2206, sensitizes endometrial cancer cells to progestin. PLoS One. 2012;7:e41593.
    1. Gu C, Zhang Z, Yu Y, et al. Inhibiting the PI3K/Akt pathway reversed progestin resistance in endometrial cancer. Cancer Sci. 2011;102:557–564.
    1. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366:520–529.
    1. Konecny GE, Santos L, Winterhoff B, et al. HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer. Br J Cancer. 2009;100:89–95.
    1. . Evaluation of carboplatin/paclitaxel with and without trastuzumab (Herceptin) in uterine serous cancer. Available at . Accessed February 12, 2016.
    1. Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–134.
    1. Reinbolt R, Hays J. The role of PARP inhibitors in the treatment of gynecologic malignancies. Front Oncol. 2013;3:237.
    1. Howitt BE, Shukla SA, Sholl LM, et al. Association of polymerase ε-mutated and microsatellite-instable endometrial cancers with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of PD-1 and PD-L1. JAMA Oncol. 2015;1:1319–1323.
    1. Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–2520.
    1. Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer. 2012;12:237–251.

Source: PubMed

3
Abonner