Release Date: 2024-06-12

Immunotherapy in Gynecologic (Ovary, Endometrium and Servics) Cancer

Sait Kitapli (Author), Ali Alkan (Author)

Release Date: 2024-06-12

Immunotherapy has shown remarkable success in treating various solid malignancies, but its application in gynecologic cancers is an evolving field. This paper provides a comprehensive overview of immunotherapy’s role in managing ovarian, endometrial, and cervical cancers. It delves into the mechanisms of immune checkpoint inhibitors, focusing on the PD-1 and CTLA-4 pathways, and their impact [...]

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    Work TypeBook Chapter
    Published inImmunotherapy in Human Cancers
    First Page219
    Last Page228
    DOIhttps://doi.org/10.69860/nobel.9786053359388.15
    Page Count10
    Copyright HolderNobel Tıp Kitabevleri
    Licensehttps://nobelpub.com/publish-with-us/copyright-and-licensing

    Immunotherapy has shown remarkable success in treating various solid malignancies, but its application in gynecologic cancers is an evolving field. This paper provides a comprehensive overview of immunotherapy’s role in managing ovarian, endometrial, and cervical cancers. It delves into the mechanisms of immune checkpoint inhibitors, focusing on the PD-1 and CTLA-4 pathways, and their impact on tumor suppression. The review highlights the challenges posed by tumor immunoediting, where cancer cells evade immune responses. It emphasizes the significance of molecular phenotyping, particularly MMR deficiency and PD-L1 expression, in predicting treatment response. There are promising results from clinical trials investigating immune checkpoint inhibitors, both as single agents and in combination with other therapies, offering potential avenues for improving outcomes in gynecologic cancer treatment.

    Sait Kitapli (Author)
    MD, Assistant Professor, Muğla Education and Research Hospital
    https://orcid.org/0000-0002-1143-1864

    Ali Alkan (Author)
    MD, Associate Professor, Muğla Education and Research Hospital
    https://orcid.org/0000-0002-8253-5046
    3Ali Alkan graduated from Marmara University School of Medicine in 2007. The same year, he started his Internal Medicine training at Hacettepe University School of Medicine. In March 2012, he earned the title of Internal Medicine Specialist and began working at Sincan State Hospital to fulfill his mandatory service. In March 2013, he started his subspecialty training in the Medical Oncology Department at Ankara University School of Medicine. He became a Medical Oncology Specialist in May 2016. Between August 2016 and September 2018, he completed his mandatory service at Osmaniye State Hospital. From June-July 2018, he worked in the Department of Palliative, Rehabilitation & Integrative Medicine at the University of Texas MD Anderson Cancer Center in Houston, USA. Currently, he is working as an Associate Professor in the Department of Medical Oncology at Muğla Sıtkı Koçman University.

    • Lynam S, Lugade AA, Odunsi K. Immunotherapy for Gynecologic Cancer: Current Applications and Future Directions. Clin Obstet Gynecol. 2020 Mar;63(1):48-63.

    • Bellmunt J, De Wit R, Vaughn DJ, Fradet Y, Lee J-L, Fong L, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. New England Journal of Medicine. 2017;376(11):1015–26.

    • Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004; 22:329–60

    • Strickland KC, Howitt BE, Shukla SA, et al. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of PD-1/PD-L1 in high-grade serous ovarian cancer. Oncotarget. 2016; 7:13587-13598.

    • Zehir A, Benayed R, Shah RH, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017; 23:703-713

    • Odunsi K. Immunotherapy in ovarian cancer. Ann Oncol, 2017;28: viii1-viii7.

    • Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. New England Journal of Medicine. 2016;375(22):2154–64

    • Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. The lancet oncology. 2017;18(9):1274–84.

    • Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K, et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proceedings of the National Academy of Sciences. 2007;104(9):3360–5.

    • Wieser V, Gaugg I, Fleischer M, Shivalingaiah G, Wenzel S, Sprung S, et al. BRCA1/2 and TP53 mutation status associates with PD-1 and PD-L1 expression in ovarian cancer. Oncotarget. 2018;9(25):17501

    • Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Murayama T, et al. Safety and antitumor activity of anti–PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. Journal of Clinical Oncology. 2015;33(34):4015–22.

    • Varga A, Piha-Paul S, Ott PA, Mehnert JM, Berton-Rigaud D, Morosky A, et al. Pembrolizumab in patients with programmed death ligand 1–positive advanced ovarian cancer: Analysis of KEYNOTE-028. Gynecologic oncology. 2019;152(2):243–50.

    • Matulonis U, Shapira-Frommer R, Santin A, Lisyanskaya A, Pignata S, Vergote I, et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Annals of Oncology. 2019.

    • Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. New England Journal of Medicine. 2015;372(26):2509–20.

    • 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.

    • Disis ML, Taylor MH, Kelly K, Beck JT, Gordon M, Moore KM, et al. Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer: phase 1b results from the JAVELIN Solid Tumor Trial. JAMA oncology. 2019;5(3):393–401.

    • Howlader N, Noone A, Krapcho M, Miller D, Brest A, Yu M, et al. SEER Cancer Statistics Review, 1975–2016, National Cancer Institute. Bethesda, MD National Cancer Institute; Bethesda, MD; 2019.

    • De Jong R, Leffers N, Boezen H, Ten Hoor K, van der Zee A, Hollema H, et al. Presence of tumor-infiltrating lymphocytes is an independent prognostic factor in type I and II endometrial cancer. Gynecologic oncology. 2009;114(1):105–1

    • Howitt BE, Shukla SA, Sholl LM, Ritterhouse LL, Watkins JC, Rodig S, et al. Association of polymerase e–mutated and microsatellite-instable endometrial cancers with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of PD-1 and PDL1. JAMA oncology. 2015;1(9):1319–23.

    • Fader A, Diaz L, Armstrong D, Tanner E, Uram J, Eyring A, et al. Preliminary results of a phase II study: PD-1 blockade in mismatch repair–deficient, recurrent or persistent endometrial cancer. Gynecologic Oncology. 2016;141:206–7. [Google Scholar]

    • Ott PA, Bang Y-J, 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. Obstetrical & Gynecological Survey. 2018;73(1):26–7.

    • Nagle CM, O’mara TA, Tan Y, Buchanan DD, Obermair A, Blomfield P, et al. Endometrial cancer risk and survival by tumor MMR status. Journal of gynecologic oncology. 2018;29(3).

    • Makker V, Rasco D, Vogelzang NJ, Brose MS, Cohn AL, Mier J, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. The Lancet Oncology. 2019;20(5):711–8

    • Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. The Journal of pathology. 1999;189(1):12–9

    • Tewari KS, Sill MW, Long III HJ, Penson RT, Huang H, Ramondetta LM, et al. Improved survival with bevacizumab in advanced cervical cancer. New England Journal of Medicine. 2014;370(8):734–43.

    • Mezache L, Paniccia B, Nyinawabera A, Nuovo GJ. Enhanced expression of P.D. L1 in cervical intraepithelial neoplasia and cervical cancers. Modern Pathology. 2015;28(12):1594.

    • Chung HC, Ros W, Delord J-P, Perets R, Italiano A, Shapira-Frommer R, et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. Journal of Clinical Oncology. 2019;37(17):1470–8

    • Naumann RW, Hollebecque A, Meyer T, Devlin M-J, Oaknin A, Kerger J, et al. Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial. Journal of Clinical Oncology.0(0): JCO.19.00739.

    • Lheureux S, Butler MO, Clarke B, Cristea MC, Martin LP, Tonkin K, et al. Association of Ipilimumab with Safety and Antitumor Activity in women with metastatic or recurrent human papillomavirus–related cervical carcinoma. JAMA oncology. 2018;4(7): e173776–e.

    • Naumann RW, Oaknin A, Meyer T, Lopez-Picazo JM, Lao C, Bang Y-J, et al. LBA62Efficacy and safety of nivolumab (Nivo) + ipilimumab (Ipi) in patients (pts) with recurrent/ metastatic (R/M) cervical cancer: Results from CheckMate 358. Annals of Oncology. 2019;30(Supplement_5)

    • Rubinstein MM, Makker V. Optimizing immunotherapy for gynecologic cancers. CurrOpin Obstet Gynecol. 2020 Feb;32(1):1-8.

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