Stage IV endometrial carcinoma: a case report on multiple biomarkers and the emerging role of immunotherapy
DOI:
https://doi.org/10.18203/2320-6012.ijrms20243729Keywords:
Endometrial carcinoma, Pembrolizumab, Lenvatinib, ImmunotherapyAbstract
Endometrial carcinoma (EC) is a common cancer with a poor prognosis in advanced stages. Despite recent development in therapies, the optimal choice for Stage IV EC with multiple mutations remains debated. Immunotherapy has come up as a promising approach, particularly targeting the PI3K/AKT/mTOR pathway, which is associated with aggressive disease. A 68-year-old African American female with a history of diabetes, hypertension, and postmenopausal bleeding was diagnosed with Stage IV B serous type endometrial carcinoma. Imaging revealed lung and lymph node metastases. The patient received 9 cycles of carboplatin and paclitaxel followed by a radical hysterectomy. Tumour profiling revealed HER2/neu amplification, PIK3CA, and TP53 mutations. Despite microsatellite stability (MSS) and proficient mismatch repair (pMMR), she was started on pembrolizumab (200 mg every 3 weeks) and lenvatinib (20 mg daily). The patient is currently in her third cycle and responding well to treatment. This case highlights the potential of immunotherapy in advanced EC with multiple biomarkers. Although pembrolizumab was initially approved for MSI-H/dMMR cases, its combination with lenvatinib has shown efficacy in pMMR/MSS patients. The case underscores the need for personalised treatment strategies based on molecular profiling, with emerging therapies targeting HER2, TP53, and PIK3CA.
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References
American Cancer Society. Cancer Facts & Figures 2024. Atlanta: American Cancer Society. 2022. Available at: https://www.cancer.org/content. Accessed on 18 August 2024.
Morice P, Leary A, Creutzberg C, Abu-Rustum N, Darai E. Endometrial cancer. The Lancet. 2016;387(10023):1094-108.
Di Tucci C, Capone C, Galati G. Immunotherapy in endometrial cancer: new scenarios on the horizon. J Gynecol Oncol. 2019;30(3):46.
Slomovitz BM, Coleman RL. The PI3K/AKT/mTOR Pathway as a Therapeutic Target in Endometrial CancerPI3K/AKT/mTOR Pathway Inhibition in Endometrial Cancer. Clinical Cancer Res. 2012;18(21):5856-64.
Ajani JA, D’Amico TA, Bentrem DJ, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Farjah F, Gerdes H, Gibson M. Esophageal and esophagogastric junction cancers, version 2.2023, NCCN clinical practice guidelines in oncology. J National Comprehensive Cancer Network. 2023;21(4):393-422.
Philp L, Kanbergs A, Laurent JS, Growdon WB, Feltmate C, Goodman A. The use of neoadjuvant chemotherapy in advanced endometrial cancer. Gynecol Oncol Rep. 2021;36:100725.
Tobias CJ, Chen L, Melamed A, St Clair C, Khoury-Collado F, Tergas AI, et al. Association of neoadjuvant chemotherapy with overall survival in women with metastatic endometrial cancer. JAMA network open. 2020;3(12):2028612.
Halla K. Emerging Treatment Options for Advanced or Recurrent Endometrial Cancer. J Adv Pract Oncol. 2022;13(1):45-59.
Di Dio C, Bogani G, Di Donato V, Cuccu I, Muzii L, Musacchio L, Scambia G, Lorusso D. The role of immunotherapy in advanced and recurrent MMR deficient and proficient endometrial carcinoma. Gynecol Oncol. 2023;169:27-33.
Santin AD, Bellone S, Gokden M. Overexpression of HER-2/neu in uterine serous papillary cancer. Clin Cancer Res. 2002;8(5):1271-9.
Cheung LW, Hennessy BT, Li J. High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability. Cancer Discov. 2012;2(8):750-1.
Juric D, Rodon J, Tabernero J, et al. Phosphatidylinositol 3-Kinase α-Selective inhibition with alpelisib (BYL719) in PIK3CA-altered solid tumors: results from the first-in-human study. J Clin Oncol. 2019;37(4):361.