Immunotherapy for Endometrial Carcinoma

Pınar KUBİLAY TOLUNAYa , Cengiz KARAÇİNa
aDr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Clinic of Medical Oncology, Ankara, Türkiye

Kubilay Tolunay P, Karaçin C. Immunotherapy for endometrial carcinoma. In: Şendur MAN, ed. Current Immunotherapy Landscape for Solid Tumors. 1st ed. Ankara: Türkiye Klinikleri; 2024. p.119-23.

ABSTRACT
Endometrial cancer is a common and fatal malignancy in women. While early-stage disease often has favorable outcomes, recurrent or metastatic endometrial cancer is challenging to treat with limited treatment options and poor survival rates. Immune checkpoint inhibitors and tyrosine kinase inhibitors are emerging therapeutic approaches for recurrent or metastatic endometrial cancer. The Cancer Genome Atlas (TCGA) has provided insights into the role of different immunotherapeutic approaches based on molecular subtypes of endometrial cancer. Immune checkpoint inhibitors have shown promise in recurrent or metastatic endometrial cancer, particularly in tumors with microsatellite instability. However, strategies to enhance response or overcome resistance to immune checkpoint inhibitors for endometrial cancer. Immunotherapy holds promise for the treatment of endometrial cancer, particularly when tailored to specific molecular subtypes and combined with other therapeutic approaches.

Keywords: Endometrial cancer; immunotherapy; immune checkpoint inhibitors

Referanslar

  1. Endometrial Cancer | Uterine Cancer [Internet]. American Cancer Society. [cited: Nov 2023, 15]. Available from: [Link]
  2. Cancer Genome Atlas Research Network; Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67-73. Erratum in: Nature. 2013;500(7461):242. [Crossref]  [PubMed]  [PMC]
  3. Xing X, Jin N, Wang J. Polymerase Epsilon-Associated Ultramutagenesis in Cancer. Cancers (Basel). 2022;14(6):1467. [Crossref]  [PubMed]  [PMC]
  4. Corr B, Cosgrove C, Spinosa D, Guntupalli S. Endometrial cancer: molecular classification and future treatments. BMJ Med. 2022;1(1):e000152. [Crossref]  [PubMed]  [PMC]
  5. Fumet JD, Truntzer C, Yarchoan M, Ghiringhelli F. Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts. Eur J Cancer. 2020;131:40-50. [Crossref]  [PubMed]  [PMC]
  6. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015;372(26):2509-20. [Crossref]  [PubMed]  [PMC]
  7. 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. [Crossref]  [PubMed]  [PMC]
  8. Mamat Yusof MN, Chew KT, Kampan NC, Shafiee MN. Expression of PD-1 and PD-L1 in Endometrial Cancer: Molecular and Clinical Significance. Int J Mol Sci. 2023;24(20):15233. [Crossref]  [PubMed]  [PMC]
  9. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409-13. [Crossref]  [PubMed]  [PMC]
  10. US FDA. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication [Internet]. U.S. Food and Drug Administration. 2017 [cited: Nov 2023, 16]. Available from: [Link]
  11. Ott PA, Bang YJ, Berton-Rigaud D, Elez E, Pishvaian MJ, Rugo HS, et al. Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death Ligand 1-Positive Endometrial Cancer: Results From the KEYNOTE-028 Study. J Clin Oncol. 2017;35(22):2535-41. [Crossref]  [PubMed]
  12. Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020;38(1):1-10. [Crossref]  [PubMed]  [PMC]
  13. Azad NS, Gray RJ, Overman MJ, Schoenfeld JD, Mitchell EP, Zwiebel JA, et al. Nivolumab Is Effective in Mismatch Repair-Deficient Noncolorectal Cancers: Results From Arm Z1D-A Subprotocol of the NCI-MATCH (EAY131) Study. J Clin Oncol. 2020;38(3):214-22. [Crossref]  [PubMed]  [PMC]
  14. 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. [Crossref]  [PubMed]  [PMC]
  15. Antill Y, Kok PS, Robledo K, Yip S, Cummins M, Smith D, et al.; Australia New Zealand Gynaecological Oncology Group (ANZGOG). 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):e002255. [Crossref]  [PubMed]  [PMC]
  16. André T, Berton D, Curigliano G, Sabatier R, Tinker AV, Oaknin A, et al. Antitumor Activity and Safety of Dostarlimab Monotherapy in Patients With Mismatch Repair Deficient Solid Tumors: A Nonrandomized Controlled Trial. JAMA Netw Open. 2023;6(11):e2341165. [Crossref]  [PubMed]  [PMC]
  17. Makker V, Colombo N, Casado Herráez A, Monk BJ, Mackay H, Santin AD, et al. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023;41(16):2904-10. [Crossref]  [PubMed]  [PMC]
  18. Eskander RN, Sill MW, Beffa L, Moore RG, Hope JM, Musa FB, et al. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N Engl J Med. 2023;388(23):2159-70. [Crossref]  [PubMed]  [PMC]
  19. Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novák Z, Black D, et al.; RUBY Investigators. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023;388(23):2145-58. [Crossref]  [PubMed]
  20. Colombo N, Harano K, Hudson E, Galli F, Antill Y, Choi CH, et al. LBA40 Phase III double-blind randomized placebo controlled trial of atezolizumab in combination with carboplatin and paclitaxel in women with advanced/recurrentendometrial carcinoma. Annals of Oncology. 2023;34:S1281-S2. [Crossref]
  21. Westin SN, Moore K, Chon HS, Lee JY, Pepin JT, Sundborg M, et al. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2023;(34 Suppl 2):S1281-S2. [Crossref]