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Erschienen in: Current Treatment Options in Oncology 8/2022

06.07.2022 | Gynecologic Cancers (JS Ferriss, Section Editor)

Incorporating Molecular Diagnostics into Treatment Paradigms for Endometrial Cancer

verfasst von: Brenna E. Swift, MD, MASc, Lilian T. Gien, MD, MSc

Erschienen in: Current Treatment Options in Oncology | Ausgabe 8/2022

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Opinion statement

The treatment of endometrial cancer has recently undergone a paradigm shift from using traditional clinical-pathologic factors to molecular characterization for prognosis and selection of treatment. Recent approval of pembrolizumab, dostarlimab, and the combination of lenvatinib and pembrolizumab has drastically changed the treatment options and response rate for advanced and recurrent endometrial cancer, especially for DNA mismatch repair–deficient (MMRd) tumors. For p53 abnormal tumors, which have the worst prognosis, there are several new treatment approaches including lenvatinib and pembrolizumab, trastuzumab, and possibly a future role for PARP inhibitors in the homologous recombination deficiency (HRD) p53 abnormal population. In DNA polymerase epsilon–mutated (POLEmut) tumors which have an excellent prognosis, there’s a possibility to de-escalate treatment, and in the small chance of recurrence, these tumors may be susceptible to immune checkpoint inhibitors. Further research is needed to better characterize biomarkers for prognosis and identify targeted treatments within the p53 wild-type (p53 WT)/no specific molecular profile (NSMP) cohort. Upcoming studies are evaluating adjuvant treatment by molecular subtype and will determine the next steps for precision medicine in endometrial cancer.
Literatur
1.
Zurück zum Zitat Getz G, Gabriel SB, Cibulskis K, Lander E, Sivachenko A, Sougnez C, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73.CrossRef Getz G, Gabriel SB, Cibulskis K, Lander E, Sivachenko A, Sougnez C, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73.CrossRef
2.
Zurück zum Zitat Talhouk A, McConechy MK, Leung S, Li-Chang HH, Kwon JS, Melnyk N, et al. A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer. 2015;113(2):299–310.PubMedPubMedCentralCrossRef Talhouk A, McConechy MK, Leung S, Li-Chang HH, Kwon JS, Melnyk N, et al. A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer. 2015;113(2):299–310.PubMedPubMedCentralCrossRef
3.
Zurück zum Zitat Talhouk A, McConechy MK, Leung S, Yang W, Lum A, Senz J, et al. Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer. Cancer. 2017;123(5):802–13.PubMedCrossRef Talhouk A, McConechy MK, Leung S, Yang W, Lum A, Senz J, et al. Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer. Cancer. 2017;123(5):802–13.PubMedCrossRef
5.
Zurück zum Zitat León-Castillo A, de Boer SM, Powell ME, Mileshkin LR, Mackay HJ, Leary A, et al. Molecular classification of the PORTEC-3 Trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy. J Clin Oncol. 2020;38(29):3388–97.PubMedPubMedCentralCrossRef León-Castillo A, de Boer SM, Powell ME, Mileshkin LR, Mackay HJ, Leary A, et al. Molecular classification of the PORTEC-3 Trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy. J Clin Oncol. 2020;38(29):3388–97.PubMedPubMedCentralCrossRef
6.
Zurück zum Zitat Prendergast EN, Holman LL, Liu AY, Lai TS, Campos MP, Fahey JN, et al. Comprehensive genomic profiling of recurrent endometrial cancer: implications for selection of systemic therapy. Gynecol Oncol. 2019;154(3):461–6.PubMedPubMedCentralCrossRef Prendergast EN, Holman LL, Liu AY, Lai TS, Campos MP, Fahey JN, et al. Comprehensive genomic profiling of recurrent endometrial cancer: implications for selection of systemic therapy. Gynecol Oncol. 2019;154(3):461–6.PubMedPubMedCentralCrossRef
7.
Zurück zum Zitat Soumerai TE, Donoghue MTA, Bandlamudi C, Srinivasan P, Chang MT, Zamarin D, et al. Clinical utility of prospective molecular characterization in advanced endometrial cancer. Clin Cancer Res. 2018;24(23):5939–47.PubMedPubMedCentralCrossRef Soumerai TE, Donoghue MTA, Bandlamudi C, Srinivasan P, Chang MT, Zamarin D, et al. Clinical utility of prospective molecular characterization in advanced endometrial cancer. Clin Cancer Res. 2018;24(23):5939–47.PubMedPubMedCentralCrossRef
8.
Zurück zum Zitat • McAlpine JN, Chiu DS, Nout RA, Church DN, Schmidt P, Lam S, et al. Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: an individual patient data meta-analysis. Cancer. 2021;127(14):2409–22. Meta-analysis of 359 women with POLEmut endometrial cancer. Disease progression and recurrence were rare and traditional prognosticators were not associated with disease progression and recurrencePubMedCrossRef • McAlpine JN, Chiu DS, Nout RA, Church DN, Schmidt P, Lam S, et al. Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: an individual patient data meta-analysis. Cancer. 2021;127(14):2409–22. Meta-analysis of 359 women with POLEmut endometrial cancer. Disease progression and recurrence were rare and traditional prognosticators were not associated with disease progression and recurrencePubMedCrossRef
9.
Zurück zum Zitat de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, et al. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2016;17(8):1114–26.PubMedCrossRef de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, et al. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2016;17(8):1114–26.PubMedCrossRef
10.
Zurück zum Zitat Van Den Heerik ASVM, Horeweg N, Nout RA, Lutgens LCHW, Van Der Steen-Banasik EM, Westerveld GH, et al. PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer. Int J Gynecol Cancer. 2020;30(12):2002–7.PubMedPubMedCentralCrossRef Van Den Heerik ASVM, Horeweg N, Nout RA, Lutgens LCHW, Van Der Steen-Banasik EM, Westerveld GH, et al. PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer. Int J Gynecol Cancer. 2020;30(12):2002–7.PubMedPubMedCentralCrossRef
13.
Zurück zum Zitat Wang F, Zhao Q, Wang YN, Jin Y, He MM, Liu ZX, et al. Evaluation of POLE and POLD1 mutations as biomarkers for immunotherapy outcomes across multiple cancer types. JAMA Oncol. 2019;5(10):1504–6.PubMedPubMedCentralCrossRef Wang F, Zhao Q, Wang YN, Jin Y, He MM, Liu ZX, et al. Evaluation of POLE and POLD1 mutations as biomarkers for immunotherapy outcomes across multiple cancer types. JAMA Oncol. 2019;5(10):1504–6.PubMedPubMedCentralCrossRef
14.
Zurück zum Zitat Mehnert JM, Panda A, Zhong H, Hirshfield K, Damare S, Lane K, et al. Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer. J Clin Invest. 2016;126(6):2334–40.PubMedPubMedCentralCrossRef Mehnert JM, Panda A, Zhong H, Hirshfield K, Damare S, Lane K, et al. Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer. J Clin Invest. 2016;126(6):2334–40.PubMedPubMedCentralCrossRef
15.
Zurück zum Zitat Garmezy B, Gheeya J, Lin HY, Huang Y, Kim T, Jiang X, et al. Clinical and molecular characterization of POLE mutations as predictive biomarkers of response to immune checkpoint inhibitors in advanced cancers . JCO Precis Oncol. 2022;(6):e2100267. Garmezy B, Gheeya J, Lin HY, Huang Y, Kim T, Jiang X, et al. Clinical and molecular characterization of POLE mutations as predictive biomarkers of response to immune checkpoint inhibitors in advanced cancers . JCO Precis Oncol. 2022;(6):e2100267.
16.
Zurück zum Zitat Veneris JT, Lee EK, Goebel EA, Nucci MR, Lindeman N, Horowitz NS, et al. Diagnosis and management of a recurrent polymerase-epsilon (POLE)-mutated endometrial cancer. Gynecol Oncol. 2019;153(3):471–8.PubMedCrossRef Veneris JT, Lee EK, Goebel EA, Nucci MR, Lindeman N, Horowitz NS, et al. Diagnosis and management of a recurrent polymerase-epsilon (POLE)-mutated endometrial cancer. Gynecol Oncol. 2019;153(3):471–8.PubMedCrossRef
17.
Zurück zum Zitat Hause RJ, Pritchard CC, Shendure J, Salipante SJ. Classification and characterization of microsatellite instability across 18 cancer types. Nat Med. 2016;22(11):1342–50.PubMedCrossRef Hause RJ, Pritchard CC, Shendure J, Salipante SJ. Classification and characterization of microsatellite instability across 18 cancer types. Nat Med. 2016;22(11):1342–50.PubMedCrossRef
18.
Zurück zum Zitat Kim SR, Pina A, Albert A, McAlpine J, Wolber R, Blake Gilks C, et al. Does MMR status in endometrial cancer influence response to adjuvant therapy? Gynecol Oncol. 2018;151(1):76–81.PubMedCrossRef Kim SR, Pina A, Albert A, McAlpine J, Wolber R, Blake Gilks C, et al. Does MMR status in endometrial cancer influence response to adjuvant therapy? Gynecol Oncol. 2018;151(1):76–81.PubMedCrossRef
19.
Zurück zum Zitat McEachron J, Zhou N, Spencer C, Chatterton C, Shanahan L, Katz J, et al. Adjuvant chemoradiation associated with improved outcomes in patients with microsatellite instability-high advanced endometrial carcinoma. Int J Gynecol Cancer. 2021;31(2):203–8.PubMedCrossRef McEachron J, Zhou N, Spencer C, Chatterton C, Shanahan L, Katz J, et al. Adjuvant chemoradiation associated with improved outcomes in patients with microsatellite instability-high advanced endometrial carcinoma. Int J Gynecol Cancer. 2021;31(2):203–8.PubMedCrossRef
20.
Zurück zum Zitat Reijnen C, Küsters-Vandevelde HVN, Prinsen CF, Massuger LFAG, Snijders MPML, Kommoss S, et al. Mismatch repair deficiency as a predictive marker for response to adjuvant radiotherapy in endometrial cancer. Gynecol Oncol. 2019;154(1):124–30.PubMedCrossRef Reijnen C, Küsters-Vandevelde HVN, Prinsen CF, Massuger LFAG, Snijders MPML, Kommoss S, et al. Mismatch repair deficiency as a predictive marker for response to adjuvant radiotherapy in endometrial cancer. Gynecol Oncol. 2019;154(1):124–30.PubMedCrossRef
21.
Zurück zum Zitat Green AK, Feinberg J, Makker V. A review of immune checkpoint blockade therapy in endometrial cancer. Am Soc Clin Oncol Educ B. 2020;40:238–44.CrossRef Green AK, Feinberg J, Makker V. A review of immune checkpoint blockade therapy in endometrial cancer. Am Soc Clin Oncol Educ B. 2020;40:238–44.CrossRef
22.
Zurück zum Zitat •• O’Malley DM, Bariani GM, Cassier PA, Marabelle A, Hansen AR, De Jesus AA, et al. Pembrolizumab in patients with microsatellite instability–high advanced endometrial cancer: results from the KEYNOTE-158 study. J Clin Oncol. 2022;40(7):752–61. KEYNOTE-158 was a phase II, single-arm trial of pembrolizumab in patients with MMRd advanced endometrial cancer showing ORR of 48%, median PFS of 13.1 months, and median OS not reachedPubMedCrossRef •• O’Malley DM, Bariani GM, Cassier PA, Marabelle A, Hansen AR, De Jesus AA, et al. Pembrolizumab in patients with microsatellite instability–high advanced endometrial cancer: results from the KEYNOTE-158 study. J Clin Oncol. 2022;40(7):752–61. KEYNOTE-158 was a phase II, single-arm trial of pembrolizumab in patients with MMRd advanced endometrial cancer showing ORR of 48%, median PFS of 13.1 months, and median OS not reachedPubMedCrossRef
23.
Zurück zum Zitat •• Oaknin A, Gilbert L, Tinker AV, Brown J, Mathews C, Press J, et al. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET - a phase I, sin. J Immunother Cancer. 2022;10(1):1–10. GARNET was a phase I, single-arm trial of dostarlimab in MMRd and MMRp in advanced and recurrent endometrial cancer showing ORR of 43.5% in MMRd, median PFS of 12.2 months, and median OS not reachedCrossRef •• Oaknin A, Gilbert L, Tinker AV, Brown J, Mathews C, Press J, et al. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET - a phase I, sin. J Immunother Cancer. 2022;10(1):1–10. GARNET was a phase I, single-arm trial of dostarlimab in MMRd and MMRp in advanced and recurrent endometrial cancer showing ORR of 43.5% in MMRd, median PFS of 12.2 months, and median OS not reachedCrossRef
24.
Zurück zum Zitat Tamura K, Hasegawa K, Katsumata N, Matsumoto K, Mukai H, Takahashi S, et al. Efficacy and safety of nivolumab in Japanese patients with uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma: multicenter, open-label phase 2 trial. Cancer Sci. 2019;110(9):2894–904.PubMedPubMedCentralCrossRef Tamura K, Hasegawa K, Katsumata N, Matsumoto K, Mukai H, Takahashi S, et al. Efficacy and safety of nivolumab in Japanese patients with uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma: multicenter, open-label phase 2 trial. Cancer Sci. 2019;110(9):2894–904.PubMedPubMedCentralCrossRef
25.
Zurück zum Zitat Antill Y, Kok PS, Robledo K, Yip S, Cummins M, Smith D, et al. Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial. J Immunother Cancer. 2021;9(6):1–8.CrossRef Antill Y, Kok PS, Robledo K, Yip S, Cummins M, Smith D, et al. Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial. J Immunother Cancer. 2021;9(6):1–8.CrossRef
26.
Zurück zum Zitat Konstantinopoulos PA, Luo W, Liu JF, Gulhan DC, Krasner C, Ishizuka JJ, et al. Phase II study of avelumab in patients with mismatch repair deficient and mismatch repair proficient recurrent / persistent endometrial cancer. J Clin Oncol. 2019;37(30):2786–94. Konstantinopoulos PA, Luo W, Liu JF, Gulhan DC, Krasner C, Ishizuka JJ, et al. Phase II study of avelumab in patients with mismatch repair deficient and mismatch repair proficient recurrent / persistent endometrial cancer. J Clin Oncol. 2019;37(30):2786–94.
27.
Zurück zum Zitat Bellone S, Roque DM, Siegel ER, Buza N, Hui P, Bonazzoli E, et al. A phase 2 evaluation of pembrolizumab for recurrent Lynch-like versus sporadic endometrial cancers with microsatellite instability. Cancer. 2022;128(6):1206–18.PubMedCrossRef Bellone S, Roque DM, Siegel ER, Buza N, Hui P, Bonazzoli E, et al. A phase 2 evaluation of pembrolizumab for recurrent Lynch-like versus sporadic endometrial cancers with microsatellite instability. Cancer. 2022;128(6):1206–18.PubMedCrossRef
31.
Zurück zum Zitat Jamieson A, Bosse T, McAlpine JN. The emerging role of molecular pathology in directing the systemic treatment of endometrial cancer. Ther Adv Med Oncol. 2021;13:1–14.CrossRef Jamieson A, Bosse T, McAlpine JN. The emerging role of molecular pathology in directing the systemic treatment of endometrial cancer. Ther Adv Med Oncol. 2021;13:1–14.CrossRef
32.
Zurück zum Zitat •• Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, et al. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med. 2022;386(5):437–48. KEYNOTE-775 was a phase III RCT of lenvatinib and pembrolizumab in MMRp and MMRd advanced endometrial cancer. In the MMRp cohort, the ORR was 30.3%, the median PFS was 6.6 months, and the median OS was 17.4 monthsPubMedCrossRef •• Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, et al. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med. 2022;386(5):437–48. KEYNOTE-775 was a phase III RCT of lenvatinib and pembrolizumab in MMRp and MMRd advanced endometrial cancer. In the MMRp cohort, the ORR was 30.3%, the median PFS was 6.6 months, and the median OS was 17.4 monthsPubMedCrossRef
33.
Zurück zum Zitat Marth C, Tarnawski R, Tyulyandina A, Pignata S, Gilbert L, Kaen D, et al. Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001. Int J Gynecol Cancer. 2022;32(1):93–100.PubMedCrossRef Marth C, Tarnawski R, Tyulyandina A, Pignata S, Gilbert L, Kaen D, et al. Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001. Int J Gynecol Cancer. 2022;32(1):93–100.PubMedCrossRef
34.
Zurück zum Zitat Fader A, Roque D, Siegel E, Buza N, Hui P, Abdelghany O, et al. Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. J Clin Oncol. 2018;10(36):2044–51.CrossRef Fader A, Roque D, Siegel E, Buza N, Hui P, Abdelghany O, et al. Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. J Clin Oncol. 2018;10(36):2044–51.CrossRef
35.
Zurück zum Zitat • Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, et al. Randomized phase II trial of carboplatin–paclitaxel compared with carboplatin–paclitaxel–trastuzumab in advanced (stage III–IV) or recurrent uterine serous carcinomas that overexpress Her2/Neu (NCT01367002): updated overall survival analysis. Clin Cancer Res. 2020;26(15):3928–35. This is a phase II RCT in advanced or recurrent HER2/neu overexpressing uterine serous carcinoma that demonstrated combination of carboplatin-paclitaxel-trastuzumab had a median PFS of 12.9 months and median OS of 29.6 months. There was even greater benefit when trastuzumab was combined with first-line chemotherapy in stage III/IV disease with a median PFS of 17.7 months and median OS not reachedPubMedPubMedCentralCrossRef • Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, et al. Randomized phase II trial of carboplatin–paclitaxel compared with carboplatin–paclitaxel–trastuzumab in advanced (stage III–IV) or recurrent uterine serous carcinomas that overexpress Her2/Neu (NCT01367002): updated overall survival analysis. Clin Cancer Res. 2020;26(15):3928–35. This is a phase II RCT in advanced or recurrent HER2/neu overexpressing uterine serous carcinoma that demonstrated combination of carboplatin-paclitaxel-trastuzumab had a median PFS of 12.9 months and median OS of 29.6 months. There was even greater benefit when trastuzumab was combined with first-line chemotherapy in stage III/IV disease with a median PFS of 17.7 months and median OS not reachedPubMedPubMedCentralCrossRef
36.
Zurück zum Zitat Erickson BK, Najjar O, Damast S, Blakaj A, Tymon-Rosario J, Shahi M, et al. Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: a multi-institutional cohort study. Gynecol Oncol. 2020;159(1):17–22.PubMedPubMedCentralCrossRef Erickson BK, Najjar O, Damast S, Blakaj A, Tymon-Rosario J, Shahi M, et al. Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: a multi-institutional cohort study. Gynecol Oncol. 2020;159(1):17–22.PubMedPubMedCentralCrossRef
37.
Zurück zum Zitat Vermij L, Horeweg N, Leon-castillo A, Rutten TA, Mileshkin LR, Mackay HJ, et al. HER2 status in high-risk endometrial cancers (PORTEC-3): relationship with histotype, molecular classification, and clinical outcomes. Cancers (Basel). 2021;13(22):1–14. Vermij L, Horeweg N, Leon-castillo A, Rutten TA, Mileshkin LR, Mackay HJ, et al. HER2 status in high-risk endometrial cancers (PORTEC-3): relationship with histotype, molecular classification, and clinical outcomes. Cancers (Basel). 2021;13(22):1–14.
40.
Zurück zum Zitat Liu JF, Xiong N, Campos SM, Wright AA, Krasner C, Schumer S, et al. Phase II study of the WEE1 inhibitor adavosertib in recurrent uterine serous carcinoma. J Clin Oncol. 2021;39(14):1531–9.PubMedCrossRef Liu JF, Xiong N, Campos SM, Wright AA, Krasner C, Schumer S, et al. Phase II study of the WEE1 inhibitor adavosertib in recurrent uterine serous carcinoma. J Clin Oncol. 2021;39(14):1531–9.PubMedCrossRef
41.
Zurück zum Zitat De Jonge MM, Auguste A, Van Wijk LM, Schouten PC, Meijers M, Ter Haar NT, et al. Frequent homologous recombination deficiency in high-grade endometrial carcinomas. Clin Cancer Res. 2019;25(3):1087–97.PubMedCrossRef De Jonge MM, Auguste A, Van Wijk LM, Schouten PC, Meijers M, Ter Haar NT, et al. Frequent homologous recombination deficiency in high-grade endometrial carcinomas. Clin Cancer Res. 2019;25(3):1087–97.PubMedCrossRef
42.
Zurück zum Zitat Post CCB, Westermann AM, Boere IA, Witteveen PO, Ottevanger PB, Sonke GS, et al. Efficacy and safety of durvalumab with olaparib in metastatic or recurrent endometrial cancer (phase II DOMEC trial). Gynecol Oncol [Internet]. 2022;165(2):223–229. Available from: https://doi.org/10.1016/j.ygyno.2022.02.025 Post CCB, Westermann AM, Boere IA, Witteveen PO, Ottevanger PB, Sonke GS, et al. Efficacy and safety of durvalumab with olaparib in metastatic or recurrent endometrial cancer (phase II DOMEC trial). Gynecol Oncol [Internet]. 2022;165(2):223–229. Available from: https://​doi.​org/​10.​1016/​j.​ygyno.​2022.​02.​025
43.
Zurück zum Zitat NRG Oncology. Testing the combination of olaparib and durvalumab, cediranib and durvalumab, olaparib and capivasertib, and cediranib alone in recurrent or refractory endometrial cancer following the earlier phase of the study that tested olaparib and cediranib in compa [Internet]. [cited 2022 Jun 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT03660826 NRG Oncology. Testing the combination of olaparib and durvalumab, cediranib and durvalumab, olaparib and capivasertib, and cediranib alone in recurrent or refractory endometrial cancer following the earlier phase of the study that tested olaparib and cediranib in compa [Internet]. [cited 2022 Jun 1]. Available from: https://​clinicaltrials.​gov/​ct2/​show/​NCT03660826
47.
Zurück zum Zitat Pfizer. Avelumab in patients with MSS, MSI-H and POLE-mutated recurrent or persistent endometrial cancer and of avelumab/talazoparib and avelumab/axitinib in patients with MSS recurrent or persistent endometrial cancer [Internet]. [cited 2022 Jun 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT02912572 Pfizer. Avelumab in patients with MSS, MSI-H and POLE-mutated recurrent or persistent endometrial cancer and of avelumab/talazoparib and avelumab/axitinib in patients with MSS recurrent or persistent endometrial cancer [Internet]. [cited 2022 Jun 1]. Available from: https://​clinicaltrials.​gov/​ct2/​show/​NCT02912572
48.
Zurück zum Zitat Karnezis AN, Leung S, Magrill J, McConechy MK, Yang W, Chow C, et al. Evaluation of endometrial carcinoma prognostic immunohistochemistry markers in the context of molecular classification. J Pathol Clin Res. 2017;3(4):279–93.PubMedPubMedCentralCrossRef Karnezis AN, Leung S, Magrill J, McConechy MK, Yang W, Chow C, et al. Evaluation of endometrial carcinoma prognostic immunohistochemistry markers in the context of molecular classification. J Pathol Clin Res. 2017;3(4):279–93.PubMedPubMedCentralCrossRef
49.
Zurück zum Zitat Travaglino A, Raffone A, Raimondo D, Reppuccia S, Ruggiero A, Arena A, et al. Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis. Arch Gynecol Obstet [Internet]. 2022;(0123456789). Available from: https://doi.org/10.1007/s00404-021-06385-0 Travaglino A, Raffone A, Raimondo D, Reppuccia S, Ruggiero A, Arena A, et al. Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis. Arch Gynecol Obstet [Internet]. 2022;(0123456789). Available from: https://​doi.​org/​10.​1007/​s00404-021-06385-0
50.
Zurück zum Zitat Kommoss FKF, Karnezis AN, Kommoss F, Talhouk A, Taran FA, Staebler A, et al. L1cam further stratifies endometrial carcinoma patients with no specific molecular risk profile. Br J Cancer. 2018;119(4):480–6.PubMedPubMedCentralCrossRef Kommoss FKF, Karnezis AN, Kommoss F, Talhouk A, Taran FA, Staebler A, et al. L1cam further stratifies endometrial carcinoma patients with no specific molecular risk profile. Br J Cancer. 2018;119(4):480–6.PubMedPubMedCentralCrossRef
51.
Zurück zum Zitat Lee SY. Tailored therapy based on molecular characteristics in endometrial cancer. Biomed Res Int. 2021;2021:2068023. Lee SY. Tailored therapy based on molecular characteristics in endometrial cancer. Biomed Res Int. 2021;2021:2068023.
52.
Zurück zum Zitat Oza AM, Elit L, Tsao MS, Kamel-Reid S, Biagi J, Provencher DM, 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(24):3278–85.PubMedPubMedCentralCrossRef Oza AM, Elit L, Tsao MS, Kamel-Reid S, Biagi J, Provencher DM, 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(24):3278–85.PubMedPubMedCentralCrossRef
53.
Zurück zum Zitat Slomovitz BM, Lu KH, Johnston T, Coleman RL, Munsell M, Broaddus RR, et al. A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma. Cancer. 2010;116(23):5415–9.PubMedCrossRef Slomovitz BM, Lu KH, Johnston T, Coleman RL, Munsell M, Broaddus RR, et al. A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma. Cancer. 2010;116(23):5415–9.PubMedCrossRef
54.
Zurück zum Zitat Slomovitz BM, Jiang Y, Yates MS, Soliman PT, Johnston T, Nowakowski M, et al. Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma. J Clin Oncol. 2015;33(8):930–6.PubMedPubMedCentralCrossRef Slomovitz BM, Jiang Y, Yates MS, Soliman PT, Johnston T, Nowakowski M, et al. Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma. J Clin Oncol. 2015;33(8):930–6.PubMedPubMedCentralCrossRef
55.
Zurück zum Zitat Soliman PT, Westin SN, Iglesias DA, Fellman BM, Yuan Y, Zhang Q, et al. Everolimus, letrozole, and metformin in women with advanced or recurrent endometrioid endometrial cancer: a multi-center, single arm, phase II study. Clin Cancer Res. 2020;26(3):581–7.PubMedCrossRef Soliman PT, Westin SN, Iglesias DA, Fellman BM, Yuan Y, Zhang Q, et al. Everolimus, letrozole, and metformin in women with advanced or recurrent endometrioid endometrial cancer: a multi-center, single arm, phase II study. Clin Cancer Res. 2020;26(3):581–7.PubMedCrossRef
57.
Zurück zum Zitat Wan JCM, Massie C, Garcia-Corbacho J, Mouliere F, Brenton JD, Caldas C, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223–38.PubMedCrossRef Wan JCM, Massie C, Garcia-Corbacho J, Mouliere F, Brenton JD, Caldas C, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223–38.PubMedCrossRef
59.
Zurück zum Zitat Makker V, Taylor MH, Oaknin A, Casado Herraez A, Orlowski R, Dutta L, et al. Characterization and management of adverse reactions in patients with advanced endometrial carcinoma treated with lenvatinib plus pembrolizumab. Oncologist. 2021;26(9):e1599–608.PubMedPubMedCentralCrossRef Makker V, Taylor MH, Oaknin A, Casado Herraez A, Orlowski R, Dutta L, et al. Characterization and management of adverse reactions in patients with advanced endometrial carcinoma treated with lenvatinib plus pembrolizumab. Oncologist. 2021;26(9):e1599–608.PubMedPubMedCentralCrossRef
60.
Zurück zum Zitat Aravantinou-Fatorou A, Andrikopoulou A, Liontos M, Fiste O, Georgakopoulou VE, Dimopoulos MA, et al. Pembrolizumab in endometrial cancer: where we stand now (review). Oncol Lett. 2021;22(6) Aravantinou-Fatorou A, Andrikopoulou A, Liontos M, Fiste O, Georgakopoulou VE, Dimopoulos MA, et al. Pembrolizumab in endometrial cancer: where we stand now (review). Oncol Lett. 2021;22(6)
Metadaten
Titel
Incorporating Molecular Diagnostics into Treatment Paradigms for Endometrial Cancer
verfasst von
Brenna E. Swift, MD, MASc
Lilian T. Gien, MD, MSc
Publikationsdatum
06.07.2022
Verlag
Springer US
Erschienen in
Current Treatment Options in Oncology / Ausgabe 8/2022
Print ISSN: 1527-2729
Elektronische ISSN: 1534-6277
DOI
https://doi.org/10.1007/s11864-022-00993-x

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